[Federal Register Volume 64, Number 245 (Wednesday, December 22, 1999)]
[Notices]
[Pages 71760-71767]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-33159]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-899; FRL-6391-1]


E.I. du Pont de Nemours and Company; Notice of Filing a Pesticide 
Petition to Establish a Tolerance for Certain Pesticide Chemicals in or 
on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

DATES: Comments, identified by docket control number PF-899, must be 
received on or before January 21, 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-899 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: James A. Tompkins (PM 25), 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; 
telephone number: (703) 305-5697; and 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            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'' 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-904. The official record 
consists of the 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 (CM #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-904 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, 401 M St., SW., 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, CM #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.

[[Page 71761]]

    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-899. 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 certain 
pesticide chemicals 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 supports 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: December 7, 1999.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petition

    The petitioner summary of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petitions was prepared by the petitioner and represents 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.

1. PP 3F4268

    EPA has received a pesticide petition (PP 3F4268) from E.I. de 
Nemours and Company (DuPont), DuPont Agricultural Products, Barley Mill 
Plaza, Wilmington, DE 19880-0038 proposing, pursuant to section 408(d) 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), 
to amend 40 CFR part 180 by establishing permanent tolerances for the 
combined residues of quizalofop-p-ester (ethyl (R)-(2-(4-((6-
chloroquinoxalin-2-yl)oxy)phenoxy)propanoate) and its acid metabolite 
quizalofop-p [R-(2-(4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)propanoic 
acid), and the S enantiomers of both the ester and the acid, all 
expressed as quizalofop-p-ethyl ester in or on the raw agricultural 
commodities foliage of legumes vegetables (except soybeans) at 3.0 
parts per million (ppm); legume vegetables (succulent or dried) group 
at 0.25 ppm; beet, sugar, molasses at 0.2 ppm; beet, sugar, root at 0.1 
ppm, and beet, sugar, top at 0.5 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The registrant has provided plant metabolism 
studies for soybeans, cotton, tomatoes, potatoes, and sugar beets. 
These studies have been previously reviewed in PP 3F4268.
    In summary, quizalofop-p ethyl ester is metabolized by cleavage at 
three sites as follows:
    i. Primary pathway is hydrolysis of the ethyl ester linkage to form 
the quizalofop-p acid, then;
    ii. Cleavage of the enol ether linkage in the acid, between the 
phenyl and quinoxalinyl rings, to form phenols, and
    iii. Cleavage of the ether between the isopropanic group and the 
phenyl ring to form a phenol.
    The plant metabolism data show that quizalofop-p ethyl ester does 
not translocate, but is rapidly hydrolyzed to the corresponding acid; 
then the phenols conjugate with the plant sugars. Metabolism studies in 
soybeans using the racemic mixture quizalofop ethyl ester and the 
resolved D+ isomer show nearly identical pathways.
    The nature of the quizalofop-p ethyl ester residue in cottonseed, 
potatoes, tomatoes, soybeans, and sugar beets is adequately understood. 
The residues of concern are quizalofop-p ethyl ester and its acid 
metabolite, quizalofop-p, and the S enantiomers of both the ester and 
the acid, all expressed as quizalofop-p ethyl ester.
    2. Analytical method. An adequate analytical methodology (high-
pressure liquid chromatography using either ultraviolet or fluorescence 
detection) is available for enforcement purposes in Vol. II of the Food 
and Drug Administration Pesticide Analytical Method (PAM II, Method I). 
There are currently no actions pending against the registration of this 
chemical. Any secondary residues expected to occur in eggs, milk, meat, 
fat, and meat byproducts of cattle, goats, hogs, horses, sheep, and 
poultry from this use will be covered by existing tolerances.

[[Page 71762]]

    Adequately validated residue analytical method, DuPont 2829 (Xenos 
Method XAM-38A, Determination of Quizalofop-P-Ethyl and its Metabolites 
in Canola, Flax, Lentils, Peas, Dry and Succulent Beans and Sugar Beet 
Tops and Roots, by Liquid Chromatography). This method determines 
residues of quizalofop-p-ethyl and its metabolites in oilseed and other 
crops. It measures levels of quizalofop-p-ethyl, quizalofop-p acid and 
conjugates as total residues in the form of 2-methoxy-6-
chloroquinoxaline (MeCHQ). Quantitation was carried out using normal 
phase high pressure liquid chromatography with fluorescence detection. 
The residues were expressed as equivalents of quizalofop-p-ethyl.
    A successful tolerance method validation (TMV) on DuPont 2829 
(Xenos Method XAM-38A) is not a prerequisite for a tolerance on beans 
(succulent and dried) as well as sugar beets and sugar beet molasses as 
there is already an enforcement method in PAM II.
    3. Magnitude of residues --i. Magnitude of the residue in plants. 
The studies submitted include field trials in three regions for 
succulent beans, six additional sites for dry beans in four regions and 
five additional sites in three regions for sugar beets.
    In conjunction with previously submitted data, an adequate amount 
of geographically representative crop field trial residue data were 
presented which show that the proposed tolerances should not be 
exceeded when quizalofop ethyl is formulated into Assure and 
used as directed.
    ii. Magnitude of the residue in animals. A ruminant feeding study 
has been submitted and reviewed by EPA. In summary, three groups of 
three lactating dairy cows (plus a control group) were fed 0.1, 0.5, 
and 5.0 ppm quizalofop ethyl ester (encapsulated) for 28 consecutive 
days. Milk was collected daily and a sub-sample was divided into skim 
milk and cream. Two cows were sacrificed after 28 days with samples of 
fat, skeletal muscle, liver, and kidney being collected and analyzed. 
The remaining cow in each test group was fed a regular diet without 
encapsulated quizalofop ethyl ester for 7 additional days before 
sacrifice. Whole milk, skim milk, and cream from the control, and the 
0.1 and 0.5 ppm dose groups showed no quizalofop to < 0.02 ppm (0.05 
ppm in cream). From the 5 ppm dose, quizalofop residues ranged from 
0.01 to 0.02 ppm in whole, and when these samples were separated into 
cream and skim milk, the quizalofop partitioned into the cream with 
residues plateauing at 0.26 to 0.31 ppm. No quizalofop to < 0.02 ppm 
was detected in skeletal muscle, and to < 0.05 ppm was detected in any 
liver or fat sample from any of the three doses. Quizalofop was 
detected in one kidney sample as 0.05 ppm from the 5 ppm dose.
    From the feed items in this petition, all of the feed items in 
cattle diets can be treated with quizalofop ethyl ester. A theoretical 
beef cattle diet consisting of canola meal, bean and pea forage, pea 
hay, and sugar beet tops which none-the-less maximizes the potential 
quizalofop exposure of 2.1 ppm. A theoretical dairy cattle diet 
consisting of pea and bean forage would none-the-less maximize the 
potential quizalofop exposure at 2.4 ppm. Substitutions of other feed 
items and varying their percentages in the diets would give a lower 
dietary quizalofop burden.
    The results of the quizalofop ethyl ester bovine feeding study show 
that finite residues will actually occur in milk and tissues from the 
feeding of quizalofop ethyl ester treated RACS or their processed feed 
items when Assure II is used as directed. The established 
quizalofop and quizalofop ethyl ester tolerance in milk, and in fat, 
meat, and meat by-products of cattle, goats, hogs, horse, and sheep are 
adequate and need not be increased from these additional uses.
    A poultry feeding study has been submitted and reviewed. In 
summary, 3 groups of 20 hens (plus 1 control group) were dosed with 
encapsulated quizalofop ethyl ester at 0.1, 0.5, and 5 ppm daily for 28 
consecutive days. Eggs were collected daily, and after 28 days 3/4 of 
the hens in each test group were sacrificed, and samples of fat, liver, 
kidney, breast and thigh muscles were collected and analyzed. Tissues 
from each test group were pooled prior to analysis. The remaining five 
hens were fed a regular poultry diet without quizalofop ethyl ester for 
an additional 7 days before sacrifice. No quizalofop residues were 
detected in the liver to < 0.05 ppm, and in breast and thigh muscles to 
< 0.02 ppm for any dose administered. From the 5 ppm dose, one kidney 
sample showed 0.09 ppm quizalofop, two fat samples were 0.05 and 0.06 
ppm quizalofop, and one egg sample was 0.02 ppm quizalofop.
    The results of the quizalofop ethyl ester poultry feeding study 
show that while it is not possible to establish with certainty whether 
finite residues will actually occur in eggs and tissues from the 
feeding of quizalofop ethyl ester treated RACS or their processed feed 
items when Assure II is used as directed, there is a 
reasonable expectation for such residues to occur. The established 
tolerance of quizalofop and quizalofop ethyl ester in eggs, and in fat, 
meat, and meat by-products of poultry are adequate and need not be 
changed from these additional uses.

B. Toxicological Profile

    1. Acute toxicity. Several acute toxicology studies were conducted 
and the overall results placed technical grade quizalofop ethyl in 
toxicity Category III. These include the following studies in Category 
III: acute oral toxicity (LD50s 1,480 and 1,670 for female 
and male rats, respectively) and eye irritation (mild effects; 
reversible within 4 days). Dermal toxicity (LD50s > 5,000 
mg/kg; rabbit), inhalation toxicity (LC50 > 5.8 mg/L; rat) 
and dermal irritation were classified within Category IV. Technical 
quizalofop ethyl was not a dermal sensitizer.
    2. Genotoxicty. Technical quizalofop ethyl was negative in the 
following genotoxicity tests: bacterial gene mutation assays with E. 
coli and S. typhimurium; gene mutation assays in Chinese hamster ovary 
(CHO) cells; in vitro DNA damage assays with B. subtillis and in rat 
hepatocytes; and an in vitro chromosomal aberration test in CHO cells.
    3. Reproductive and developmental toxicity. Studies supporting the 
registration include: A developmental toxicity study in rats 
administered dosage levels of 0, 30, 100, and 300 mg/kg/day highest 
dose tested (HDT). The maternal toxicity no observed adverse effect 
level (NOAEL) was 30 mg/kg/day and a developmental toxicity NOAEL was 
greater than 300 mg/kg/day (HDT). The maternal NOAEL was based on 
reduced food consumption and increased liver weights.
    A developmental toxicity study in rabbits administered dosage 
levels of 0, 7, 20, and 60 mg/kg/day with no developmental effects 
noted at 60 mg/kg/day (HDT). The maternal toxicity NOAEL was 20 mg/kg/
day based on decreases in food consumption and body weight gain at 60/
mg/kg/day (HDT).
    A 2-generation reproduction study in rats fed diets containing 0, 
25, 100, or 400 ppm (or approximately 1, 1.25, 5, and 20 mg/kg/day, 
respectively) with a developmental (systemic effects) NOAEL of 1.25 mg/
kg/day for F2B weanlings based on increased liver weights 
and increased incidence of eosinophilic changes in the livers at 5.0 
mg/kg/day. These liver changes were considered to be physiological or 
adaptive changes to compound exposure among weanlings. When access to 
the mother's feed is available, it is a common observation that young 
rats will begin consuming chow prior to

[[Page 71763]]

complete weaning at 21 days of age. Consumption could not be 
quantified; therefore, the maternal consumption was assumed as the 
NOAEL (if normalized on a body weight basis, exposures to the weanling 
rats were likely higher). The parental NOAEL of 5.0 mg/kg/day was based 
on decreased body weight and premating weight gain in males at 20 mg/
kg/day (HDT).
    4. Subchronic toxicity. A 90-day study was conducted in rats fed 
diets containing 0, 40, 128, 1,280 ppm (or approximately 0, 2, 6.4, and 
64 mg/kg/day, respectively). The NOAEL was 2 mg/kg/day. This was based 
on increased liver weights at 6.4 mg/kg.
    A 90-day feeding study in mice was conducted with diets that 
contained 0, 100, 316, or 1,000 ppm (or approximately 0, 15, 47.4, and 
150 mg/kg/day, respectively). The NOAEL was < 15 mg/kg/day lowest dose 
tested (LDT) based on increased liver weights and reversible 
histopathological effects in the liver at the LDT.
    A 6-month feeding study in dogs was conducted with diets that 
contained 0, 25, 100, or 400 ppm (or approximately 0, 0.625, 2.5, and 
10 mg/kg/day, respectively). The NOAEL was 2.5 mg/kg/day based on 
increased blood urea nitrogen at 10 mg/kg/day.
    A 21-day dermal study was conducted in rabbits at doses of 0, 125, 
500, or 2,000 mg/kg/day. The NOAEL was 2,000 mg/kg/day (HDT).
    5. Chronic toxicity. An 18-month carcinogenicity study was 
conducted in CD-1 mice fed diets containing 0, 2, 10, 80, or 320 ppm 
(or approximately 0, 0.3, 1.5, 12, and 48 mg/kg/day, respectively). 
There were no carcinogenic effects observed under the conditions of the 
study at levels up to and including 12 mg/kg/day. A marginal increase 
in the incidence of hepatocellular tumors was observed at 48 mg/kg/day, 
the HDT, which exceeded the maximum tolerated dose (MTD). (See the 
discussion by the EPA HED Carcinogenicity Peer Review Committee below.)
    A 2-year chronic toxicity/carcinogenicity study was conducted in 
rats fed diets containing 0, 25, 100 or 400 ppm (or 0, 0.9, 3.7, and 
15.5 mg/kg/day for males and 0, 1.1, 4.6, and 18.6 mg/kg/day for 
females, respectively). There were no carcinogenic effects observed 
under the conditions of the study at levels up to and including 18.6 g/
kg/day (HDT). The systemic NOAEL was 0.9 mg/kg/day based on altered red 
cell parameters and slight/minimal centrilobuler enlargement of the 
liver at 3.7 mg/kg/day.
    A 1-year feeding study was conducted in dogs fed diets containing 
0, 25, 100, or 400 ppm (or approximately 0, 0.625, 2.5, and 10 mg/kg/
day, respectively). The NOAEL was 10 mg/kg/day (HDT).
    The Carcinogenicity Peer Review Committee (CPRC) of EPA HED has 
evaluated the rat and mouse cancer studies on quizalofop along with 
other relevant short-term toxicity studies, mutagenicity studies, and 
structure activity relationships. The CPRC concluded, after three 
meetings and an evaluation by the OPP Science Advisory Panel (SAP), 
that the classification should be a Category D (not classifiable as to 
human cancer potential). No new cancer studies were required.
    The first CPRC review tentatively concluded that quizalofop should 
be classified as a Category B2 (probable human carcinogen). That 
classification was based on liver tumors in female rats, ovarian tumors 
in female mice, and liver tumors in male mice. This classification was 
downgraded to a Category C (possible human carcinogen) at a second CPRC 
review. The change in classification was due to a reexamination of the 
liver tumors in female rats and ovarian tumors in female mice. The 
first peer review had found a statistically significant positive trend 
for liver carcinomas in female rats. Subsequent to this conclusion the 
tumor data was reevaluated, and the revaluation showed a reduced number 
of carcinomas. Although there remained a statistically significant 
positive trend for carcinomas in the study, the CPRC concluded that the 
carcinomas were not biologically significant given the few carcinomas 
identified (one at the mid-dose and two at the high dose). Noting that 
this level of carcinomas was within historical levels, the CPRC 
concluded that administration of quizalofop did not appear to be 
associated with the liver carcinomas.
    As to the ovarian tumors in female mice, the CPRC had first 
attached importance to the fact that these tumors were statistically 
significant at the high dose as compared to historical control values 
although statistically significant when compared to concurrent 
controls. However, review of further historical control data showed 
that the level of ovarian tumors in the quizalofop study was similar to 
the background rate in several other studies. Given this information 
and that the quizalofop study showed no hyperplasia of the ovary, no 
signs of endocrine activity related to ovarian function, and no dose 
response relationship, the CPRC concluded that the ovarian tumors were 
probably not compound-related.
    The findings of the second CPRC review were presented to EPA's SAP. 
The SAP concurred with the CPRC conclusion that the liver tumors in 
female rats and the ovary tumors in female mice showed no evidence of 
carcinogenicity. However, the SAP disagreed with CPRC's classification 
of quizalofop as a Category C based on the liver tumors in male mice. 
The SAP concluded that the mouse liver tumors did not support such a 
classification because the tumors occurred at a dose above the MTD and 
because they were not statistically significant if a ``p'' value of 
less than 0.05. The SAP believed that such greater statistical rigor 
was appropriate for variable tumor endpoints such as male mouse liver 
tumors.
    Following the SAP review, the CPRC changed the classification for 
quizalofop to Category D. The Category D classification is based on an 
approximate doubling in the incidence of male mice liver tumors between 
controls an the high dose. This finding was not considered strong 
enough to warrant the finding of a Category C (possible human 
carcinogen) since the increase was of marginal statistical 
significance, occurred at a high dose which exceeded the predicted MTD, 
and occurred in a study in which the concurrent control for liver 
tumors was somewhat low as compared to the historical controls; while 
the high dose control group was at the upper end of previous historical 
control-groups.
    EPA has found the evidence on the carcinogenicity of quizalofop-p 
ethyl ester in animals to be equivocal and therefore concludes that 
quizalofop-p ethyl ester does not induce cancer in animals within the 
meaning of the Delaney clause. Important to this conclusion was the 
following evidence:
    i. The only statistically significant tumor response that appears 
compound-related was seen at a single dose in a single sex in a single 
species.
    ii. The response was only marginally statistically significant.
    iii. The response was only significant when benign and malignant 
tumors were combined.
    iv. The tumors were in the male mouse liver.
    v. The tumors were within historical controls.
    vi. The mutagenicity studies were negative.
    Although in some circumstances a finding of animal carcinogenicity 
would be made despite any one, or even several, of the six factors 
noted, the combination of all of these factors here cast sufficient 
doubt on the reproducibility of the response in the high dose male 
mouse that EPA concludes the evidence on carcinogenicity is equivocal.

[[Page 71764]]

    6. Animal metabolism. The metabolism of quizalofop ethyl in animals 
(rat, goat and poultry) is well understood. 14C-phenyl and 
14C-quinoxaline quizalofop ethyl ester metabolism studies 
have been conducted in each species. There are similarities among these 
species with respect to metabolism. Quizalofop ethyl is rapidly and 
extensively metabolized and rapidly excreted by rats. The principal 
metabolites were the quizalofop-p acid and two dechlorinated 
hydroxylated forms of the acid. Tissue residues were minimal and there 
was no evidence of accumulation of quizalofop ethyl or its metabolites 
in the rat.
    The primary pathway in ruminants is hydrolysis of the ethyl ester 
to form the quizalofop-p methyl ester. In poultry, the primary 
metabolic pathway is also the hydrolysis of the ethyl ester to form the 
quizalofop-p acid, then the methyl esterification to form the 
quizalofop methyl ester becomes a minor pathway.
    The nature of the quizalofop ethyl ester residue in livestock is 
adequately understood. The residues of concern are quizalofop ethyl, 
quizalofop methyl, and quizalofop, all expressed as quizalofop ethyl.
    7. Metabolite toxicology. There is no evidence that the metabolites 
of quizalofop ethyl as identified as either the plant or animal 
metabolism studies are of any toxicological significance.
    8. Endocrine disruption. No special studies investigating potential 
estrogenic or other endocrine effects of quizalofop p-ethyl have been 
conducted. However, the standard battery of required toxicology studies 
has been completed. These include an evaluation of the potential 
effects on reproduction and development, and an evaluation of the 
pathology of the endocrine organs following repeated or long-term 
exposure to doses that far exceed likely human exposures. Based on 
these studies there is no evidence to suggest that quizalofop p-ethyl 
has an adverse effect on the endocrine system.

C. Aggregate Exposure

    1. Dietary exposure. An analysis of chronic dietary risk was 
conducted to determine the total exposure from current and proposed 
final tolerances for quizalofop-p-ethyl. A Reference Dose (RfD) of 
0.009 mg/kg/day was used in the analyses.
    i. Food. The first step in the analysis was to run the TAS 
(Tolerance Assessment System) program using current tolerances with an 
RfD of 0.009 mg/kg/day. The Theoretical Maximum Residue Concentration 
(TMRC), based on the current tolerances, was 0.000318 mg/kg/day for the 
U.S. population (48 contiguous States) and 0.000814 mg/kg/day for the 
population subgroup with the highest estimated exposure (children 1-6 
yrs. old). For the U.S. population subgroup this represents 
approximately 3.5% of the RfD while for the most exposed population 
this represents approximately 9.0% of the RfD. Based on the risk 
estimates arrived at in this analysis, chronic dietary risk from the 
current uses of Assure is minimal.
    ii. Drinking water. Another potential source of dietary exposure to 
pesticides is residues in drinking water. There is no established 
Maximum Concentration Level (MCL) for quizalofop ethyl in water. Based 
on the low use rate of quiza lofop ethyl, and a use pattern that is not 
widespread (since the current and proposed uses are on minor crops), 
DuPont does not anticipate residues of quizalofop in drinking water and 
exposure from this route is unlikely.
    2. Non-dietary exposure. Quizalofop ethyl is not registered for any 
use that could result in non-occupational, non-dietary exposure to the 
general population.

D. Cumulative Effects

    There is no evidence to indicate or suggest that quizalofop p-ethyl 
has any toxic effects on mammals that would be cumulative with those of 
any other chemicals.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above and based on the most sensitive species chronic NOAEL 
of 0.9 mg/kg and a RfD of 0.009 mg/kg/day, the existing tolerances and 
proposed uses of quizalofop ethyl are expected to utilize 3.5% of the 
RfD for the general U.S. population. Generally, exposures below 100% of 
the RfD are of no concern because the RfD represents the level at or 
below which daily aggregate dietary exposure over a lifetime will not 
pose risk to human health. Thus, there is a reasonable certainty that 
no harm will result from aggregate exposure to quizalofop ethyl 
resulting from current and proposed agricultural uses.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of quizalofop ethyl, 
data were considered from developmental toxicity studies in the rat and 
rabbit, and a multi-generation reproduction study in rats. There were 
no developmental effects observed in the absence of maternal toxicity 
in the rat and rabbit developmental studies. Minimal adaptive or 
physiological effects were observed in livers of weanlings in the 2-
generation rat reproduction study described earlier. However, this 
effect was only observed at a dose that far exceeds any expected human 
exposure. Further, the NOAEL of 0.9 mg/kg/day from the 2-year rat study 
with quizalofop ethyl which was used to calculate the RfD (discussed 
above), is already lower than any of the NOAELs defined in the 
developmental and reproductive toxicity studies with quizalofop ethyl.
    As indicated above, infants and children have a low potential for 
quizalofop ethyl exposure. The toxicology profile of quizalofop ethyl 
demonstrates low mammalian toxicity. Because there was no evidence that 
offspring were uniquely susceptible to the toxic effects of quizalofop 
ethyl, an additional 10-fold uncertainty factor should not be required 
to protect infants and children. Therefore, the RfD of 0.009 mg/kg/day, 
which utilizes a 100-fold safety factor, is appropriate to assure a 
reasonable certainty of no harm to infants and children from aggregate 
exposure to quizalofop ethyl.

F. International Tolerances

    Since there are no Mexican or Codex MRLs/tolerances, compatibility 
is not a problem at this time. Compatibility cannot be achieved with 
the Canadian negligible residue type limit at 0.1 ppm at the USA use 
pattern, which had findings of real residues above 0.1 ppm.

2. PP 4F4278

    EPA has received a pesticide petition (PP 4F4278) from E.I. DuPont 
de Nemours and Company, DuPont Agricultural Products, Barley Mill 
Plaza, Wilmington, DE 19880-0038 proposing, pursuant to section 408(d) 
of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by 
establishing tolerances for residues of triflusulfuron methyl: Methyl 2 
[[[[[4-(dimethylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-
yl]amino]carbonyl]amino]sulfonyl]-3-methylbenzoate in or on the raw 
agricultural commodity [beet, sugar, root and beet, sugar, top at 0.05 
parts per million (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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. Metabolism of triflusulfuron methyl in sugar 
beets was

[[Page 71765]]

studied using triflusulfuron methyl labeled separately with carbon-14 
in the triazine ring and in the ester carbonyl group. Triflusulfuron 
methyl was extensively metabolized by sugar beets treated at the 4-8-
leaf growth stage with 100 grams active ingredient per half acre (g ai/
ha). Triflusulfuron methyl levels dropped rapidly from  3 ppm in the 
sample taken on the day of the treatment to < 0.01 ppm 14 days after 
treatment. The initial step in the metabolic breakdown of 
triflusulfuron methyl involves cleavage of the sulfonylurea bridge, 
which is followed by further metabolism of the initial degradates. The 
levels of principal radiolabeled metabolites found in plant samples (N-
desmethyl triazine amine, N,N-bis-desmethyl triazine amine, acid 
sulfonamide, and its glucose conjugate) dropped to < 0.01 ppm at 
maturity. No significant (> 0.01 ppm) residues of triflusulfuron methyl 
or its radiolabeled metabolites were detected in mature roots or 
foliage.
    2. Analytical method. A method for quantitation of triflusulfuron 
methyl in sugar beets uses a high performance liquid chromatograph 
(HPLC) with eluent and column-switching and ultra-violet (UV) detection 
at 232 nm for the determination of triflusulfuron methyl residues in 
sugar beet foliage and roots. Sample clean-up is achieved through 
reversed phase chromatography using eluent-switching. Column-switching 
provides the resolution required for quantitation of triflusulfuron 
methyl. The method allows for quantitation of triflusulfuron methyl in 
sugar beet foliage and roots at levels as low as 0.02 ppm based on a 
10-gram sample. Triflusulfuron methyl is detected at levels as low as 
0.005 ppm. Triflusulfuron methyl recoveries averaged 98% for forage and 
101% for roots.
    3. Magnitude of residues. Triflusulfuron methyl degraded rapidly in 
sugar beets to produce the triazine amine which undergoes consecutive 
demethylations to yield N-desmethyl triazine amine and N,N-bis-
desmethyl triazine amine. Residues of triflusulfuron methyl at harvest 
were below the detection limits in sugar beet roots and foliage at all 
application levels. There is no reasonable expectation of residues of 
triflusulfuron methyl occurring in sugar beet roots or foliage at 
harvest. The data supports a preharvest interval of 30 days.
    Residues of the metabolite triazine amine and N-desmethyl triazine 
amine were at or below the detection limit of 0.02 ppm in sugar beet 
roots and foliage at all application levels at all test sites. Residues 
of N,N-bis-desmethyl triazine amine were below the detection limit of 
0.02 ppm in roots at all application levels at all locations; however, 
residues in foliage were detected in 7 out of 41 samples at up to 0.05 
ppm in samples that were treated at exaggerated rates (70 g ai/ha/
application). At the expected maximum seasonal use rate of 60 g ai/ha, 
residues of N,N-bis-desmethyl triazine amine are not expected above the 
0.02 ppm detection limit.
    The potential of triflusulfuron methyl residues occurring during 
processing of sugar beet roots treated with triflusulfuron methyl was 
also determined. Samples of sugar beet roots, harvested at maturity 
from plots treated with triflusulfuron methyl at a rate of 420 g ai/ha, 
were processed. Triflusulfuron methyl was below the 0.01 ppm detection 
limit in sugar beet root and all the processed fractions (sugar, 
molasses, and dried pulp). The lack of concentration of triflusulfuron 
methyl even at the exaggerated dose used in this study confirms that at 
the proposed use rate of triflusulfuron methyl, there is no reasonable 
expectation of residues in sugar beet roots or processed fractions.

B. Toxicological Profile

    1. Acute toxicity. Based on EPA criteria, technical triflusulfuron 
methyl is in acute toxicity Category IV for oral and inhalation routes 
of exposure, and for dermal irritation. Triflusulfuron methyl is in 
acute toxicity Category III for dermal toxicity and for eye irritation.

 
 
 
 
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 > 5.1 mg/L
Primary eye irritation in rabbits           Non-irritant
Primary dermal irritation in rabbits        Non-irritant
Dermal sensitization in guinea pigs         Non-sensitizer
Acute Neurotoxicity                         (NOAEL) = 2,000 mg/kg/day
                                             highest dose tested (HDT)
 


    2. Genotoxicty. Mutagenicity data technical triflusulfuron methyl 
include a reverse mutation assay (Ames Test) which was negative at 
concentrations up to 1,000 g/plate, the highest level tested; 
a Salmonella typhimurium plate incorporation assay which was negative 
at concentrations up to 3,000 g/plate, the highest level 
tested; a Chinese hamster ovary/hypoxanthine-guanine (CHO/HPRT) assay 
which was negative at concentrations up to 2,000 mg/kg/day, the highest 
level tested. A chromosomal aberration/human lymphocyte assay was 
positive in the presence of metabolic activation at concentrations 
greater than or equal to 1,500 g/mL. A second chromosomal 
aberration/human lymphocyte assay was positive in the presence of 
metabolic activation at concentrations of 2,000 g/mL. Results 
in the absence of metabolic activation were inconclusive for both 
chromosomal aberration studies. The mouse bone marrow micronucleus test 
was negative at doses up to 5,000 mg/kg, the highest dose level tested. 
In three Salmonella typhimurium plate incorporation assays, metabolites 
of triflusulfuron methyl were negative up to 5,000 g/plate, 
the highest level tested.
    3. Reproductive and developmental toxicity. In a 2-generation rat 
reproduction study rats were fed dosages of 0, 0.588, 5.81, 44.0 and 
89.5 mg/kg/day (males) and 0, 0.764, 7.75, 58.0, and 115 mg/kg/days 
(females) with a reproductive toxicity NOAEL equal to or greater than 
89.5 and 115 mg/k/day for males and females, respectively, based on the 
absence of reproductive effects in rats at the highest dose level. The 
NOAEL for systemic toxicity was 5.81 and 7.75 for males and females, 
respectively based on decreased body weight/body weight gain and food 
efficiency in males and females, and decreased weights of offspring 
from the F0 generation on days 14 and 21 post-partum at 44.0 
and 58.0 mg/kg/day in males and females, respectively.
    Technical triflusulfuron methyl was evaluated for developmental 
toxicity potential in rats and rabbits. Rats were fed dosages of 0, 30, 
120, 350, and 1,000 mg/kg/day with a developmental NOAEL equal to or 
greater than 1,000 mg/kg/day (HDT) and a maternal toxicity NOAEL of 120 
mg/kg/day with a lowest observed adverse effect level (LOAEL) of 350 
mg/kg/day based on reduced body weight gain in the 350 and 1,000 mg/kg/
day animals, reduced food consumption in the 1,000 mg/kg/day animals 
and lower food efficiency in the 350 and 1,000 mg/kg/day.
    Rabbits were fed dosages of 0, 15, 90, 270, and 800 mg/kg/day with 
a NOAEL for developmental toxicity of 90 mg/kg/day with a LOAEL of 270 
mg/kg/day based on the increase in abortions and a decrease in mean 
fetal body weight. The NOAEL for maternal toxicity is 90 mg/kg/day with 
a LOAEL of 270 mg/kg/day based on the maternal death and abortions, and 
increase in clinical signs noted in the mid-high and high dose groups, 
decreased food efficiency and

[[Page 71766]]

increased post mortem finding describing gastrointestinal effects.
    4. Subchronic toxicity. The subchronic toxicity of technical 
triflusulfuron methyl was evaluated in rabbits, rats, and dogs. In a 
21-day dermal toxicity study with rabbits fed dosages of 50, 300, or 
1,000 mg/kg/day, the systemic toxicity NOAEL was equal to or greater 
than 1,000 mg/kg/day for males and females. The dermal toxicity NOAEL 
was equal to or greater than 1,000 mg/kg/day for males and females.
    Two 90-day studies were conducted in the rat. In one study, rats 
were fed dosages of 6.2, 127, 646, or 965 mg/kg/day (males) or 7.54, 
150, 774, or 1,070 mg/kg/day (females). Triflusulfuron methyl exhibited 
subchronic toxicity at dietary concentrations of 2,000 ppm (127 and 150 
mg/kg/day for males and females) or greater in the form of decreased 
body weights, decreased body weight gains, decreased food efficiency, 
increased mean relative liver weights, and regenerative anemia. The 
NOAEL was 6.2 mg/kg/day (males) and 7.54 mg/kg/day(females). In another 
study, rats were fed dosages of 6.56, 133, 658, or 1,036 mg/kg/day 
(males) or 7.71, 153, 783, or 1,124 mg/kg/day (females). Triflusulfuron 
methyl showed subchronic toxicity at dietary concentrations of 2,000 
ppm (133 and 153 mg/kg/day for males and females) or greater in the 
form of decreased body weight, decreased body weight gain, decreased 
food efficiency, and increased mean liver weights. The NOAEL was 6.56 
mg/kg/day (males) and 7.71 mg/kg/day (females).
    A subchronic neurotoxicity study with rats fed dosages of 0, 6.1, 
46.1, 92.7, or 186.2 mg/kg/day (males) or 7.1, 51.6, 104.1, or 205.2 
mg/kg/day (females), resulted in a NOAEL of 92.7 (males) and 7.1 mg/kg/
day (females). This was based on decreased body weight/body weight gain 
at the lowest observed effect level of 186.2 mg/kg/day (males) and 51.6 
mg/kg/day (females).
    In another 90-day subchronic study, dogs were fed dosages of 3.87, 
146.1, or 267.6 mg/kg/day (males) or 3.72, 159.9, or 250.7 mg/kg/day 
(females). Triflusulfuron methyl was found to be hepatotoxic at 4,000 
ppm (146.1 mg/kg/day males and 159.9 mg/kg/day (females), and greater 
(elevated hepatic enzyme levels and postmortem evidence, including 
elevation in liver weights and microscopic evidence of bile stasis). 
Other microscopic findings considered to be treatment related were 
testicular atrophy and decreased testicular weights and 
hypercellularity of the sternal and femoral bone marrow, with a 
corresponding increase in reticulocyte and leukocyte counts seen in the 
high-dose males and females. Based on the microscopic findings in the 
liver and testes of the 4,000 ppm and greater treated animals, the 
NOAEL was 3.87 mg/kg/day (males) and 3.72 mg/kg/day (females).
    5. Chronic toxicity. The chronic toxicity of technical 
triflusulfuron methyl was evaluated in dogs, mice, and rats. In a 1-
year oral toxicity study with dogs fed dosages of 1.0, 26.9, 111.6 mg/
kg/day (males) and 1.2, 27.7, and 95.5 mg/kg/day (females), the NOAEL 
for males was 26.9 mg/kg/day; this was based on increases in alkaline 
phosphatase, liver weight, and incidence of minimal centrilobular 
hypertrophy at the LOAEL of 111.6. For females, the NOAEL was 27.7 mg/
kg/day; this was based on increased liver weight and increased 
incidence of minimal centrilobular hepatocellular hypertrophy at the 
LOAEL of 95.5 mg/kg/day.
    In an 18-month carcinogenicity study, mice were fed dosages of 
1.37, 20.9, 349, and 1,024 mg/kg/day (males) and 1.86, 27.7, 488, and 
1,360 mg/kg/day (females). Male mice had statistically significant 
positive trends for hepatocellular adenomas and for combined adenoma/
carcinoma (driven entirely by adenomas) at 349 and 1,024 mg/kg/day. 
These increases were not significant in pair-wise comparisons with 
control groups and were determined not to be carcinogenic effects by 
the Carcinogenicity Peer Review Committee (CPRC). The NOAEL was based 
on body and organ weight effects and was 20.9 mg/kg/day (males) and 
27.7 mg/kg/day (females).
    In the combined chronic toxicity/carcinogenicity study rats were 
fed dosages of 0, 0.406, 4.06, 30.6 and 64.5 mg/kg/day (males) and 0, 
0.546, 5.47, 41.5, and 87.7 mg/kg/day (females). Male rats have a 
significant increasing trend and significant differences in pair-wise 
comparisons of the 30.6 and 64.5 mg/kg/day dose groups with controls 
for interstitial cell adenomas. This effect was determined to be a 
carcinogenic effect by the CPRC. No carcinogenic effects were noted in 
females up to and including 87.7 mg/kg/day (highest dose tested). The 
LOAEL for chronic toxicity is 30.6 mg/kg/day (males) and 41.5 (females) 
based on decreased body weight and body weight gain, alternations in 
the hematology parameters (males predominately) and an increased 
incidence of interstitial cell hyperplasia in males. The NOAEL for 
chronic toxicity is 4.06 mg/kg/day (males) and 5.47 mg/kg/day 
(females). This value is adjusted to the lowest concentration level of 
the chemical at this dosage (60%), resulting in NOAELs of 2.44 mg/kg/
day (males) and 3.28 mg/kg/day (females).
    6. Animal metabolism. For triflusulfuron methyl, in both the rat 
and the goat, a majority of the administrated dose was excreted in 
feces and urine. The biotransformation pathway for triflusulfuron 
methyl in the rat and the goat was similar. The major pathway was 
demethylation of the dimethylamino substituent on the triazine ring. 
The intermediate hydroxylated metabolite was also present. The 
secondary biotransformation pathway was clevage of the sulfonylurea 
bridge to form methyl saccharin, N-desmethyl triazine amine and N,N-
bis-desmethyl triazine amine. In the lactating goat, triflusulfuron 
methyl was not excreted to any appreciable level in the milk. Levels of 
the ester carbonyl-derived residues were generally below the limit of 
reliable measurement (< 0.0006 g equivalent triflusulfuron 
methyl/mL) and triazine-derived residues reached a daily level of about 
0.001 ppm.
    Therefore, the metabolic pathways in rats and lactating goats were 
very similar. There were no significant plant metabolites of 
triflusulfuron methyl that were not found in the rat or goat metabolism 
studies. In the unlikely event that triflusulfuron methyl were to enter 
the livestock diet, triflusulfuron methyl and its metabolites would be 
rapidly excreted and would not accumulate in meat, meat by-products, or 
milk.
    7. Metabolite toxicology. The approximate lethal dose (ALD) of the 
degradation product, N,N-bis-desmethyl triazine amine, in male rats was 
450 mg/kg/day. Rats were fed dose rates of 200, 300, 450, 670, 1,000, 
and 2,300 mg/kg of triflusulfuron methyl. Deaths occurred up to test 
day 7 in rats dosed at 450 mg/kg body weight and above. Clinical signs 
of toxicity were observed in lethally and nonlethally dosed rats. In an 
in vitro gene mutation study, N,N,-bis-desmethyl triazine amine was not 
mutagenic in Salmonella typhimurium up to a dose of 5,000 g/
plate.
    For the degradation product, triazine amine, the ALD in male rats 
was 670 mg/kg/day. The test substance dose was 200, 300, 450, 670, 
1,000, or 2,300 mg/kg. Deaths occurred up to test day 4 in rats dosed 
at 670 mg/kg and above. Clinical signs of toxicity were observed in 
lethally and nonlethally dosed animals. In an in vitro gene mutation 
study, triazine amine was not mutagenic in Salmonella typhimurium up to 
a dose of 5,000 g/plate.
    8. Endocrine disruption. No special studies investigating potential 
estrogenic or other endocrine effects of

[[Page 71767]]

triflusulfuron methyl have been conducted. However, the standard 
battery of required toxicology studies have been completed. These 
include an evaluation of the potential effects on reproduction and 
development, and an evaluation of the pathology of the endocrine organs 
following repeated or long-term exposure to doses that far exceed 
likely human exposures. Based on these studies there is no evidence to 
suggest that triflusulfuron methyl has an adverse effect on the 
endocrine system.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. The acute dietary exposure was 
estimated for triflusulfuron methyl using the Dietary Exposure 
Evaluation Model (version 6.73) for a number of subpopulation groups. 
An acute Tier I dietary analysis was based upon the residues for sugar 
beet (root) at 0.05 ppm and sugar beet (top) at 0.05 ppm. The acute 
reference dose (aRfD) is 0.9 mg/kg bw/day (based upon a NOAEL of 90 mg/
kg bw/day and a 100-fold safety factor). For triflusulfuron methyl, the 
predicated exposure for the U.S. population was 0.00460 mg/kg bw/day 
(0.05 % of the aRfD) at the 95th percentile. The subpopulation with the 
highest predicted exposure was the non-nursing infants subgroup with an 
exposure of 0.00166 mg/kg bw/day (0.19% of the aRfD) at the 95th 
percentile. Because the predicted exposures, expressed as percentages 
of the aRfD, are well below 100%, there is reasonable certainty that no 
acute effects would result from dietary exposure to triflusulfuron 
methyl.
    The chronic dietary exposure was estimated for triflusulfuron 
methyl using the Dietary Exposure Evaluation Model (version 6.74) for a 
number of subpopulation groups. A chronic Tier I dietary analysis was 
based upon residues for sugar beet (root) at 0.05 ppm and sugar beet 
(top) at 0.05 ppm. The chronic RfD is 0.024 mg/kg bw/day (based upon a 
NOAEL of 2.44 mg/kg bw/day and a safety factor of 100). The estimated 
exposure for the U.S. population was 0.000146 mg/kg bw/day (0.6% of the 
RfD). For the subpopulation with the highest level of exposure (non-
nursing infants), the exposure was 0.000433 mg/kg bw/day (>1.8% of the 
chronic reference dose (cRfD)). Because the predicted exposures, 
expressed as percentages of the cRfD, are well below 100%, there is 
reasonable certainty that no chronic effects would result from dietary 
exposure to triflusulfuron methyl.
    Even though very conservative assumptions were made in predicting 
acute and chronic exposures to triflusulfuron methyl, the predicted 
exposures expressed as percentages of the cRfD and aRfD values were 
found to be well within the acceptable range.
    ii. Drinking water. Another potential source of dietary exposure is 
residues in drinking water. Based on the available environmental 
studies conducted with triflusulfruon methyl, DuPont concludes that 
there is no anticipated exposure to residues of triflusulfuron methyl 
in drinking water. In addition, there is no established maximum 
concentration level (MCL) for residues of triflusulfuron methyl in 
drinking water.
    2. Non-dietary exposure. Triflusulfuron methyl is not registered 
for any use that could result in non-occupational or non-dietary 
exposure to the general population.

D. Cumulative Effects

    Triflusulfuron methyl belongs to the sulfonylurea class of crop 
protection chemicals. Other structurally similar compounds in this 
class are registered herbicides. However, the herbicidal activity of 
sulfonylureas is due to the inhibition of acetolacate synthase (ALS), 
an enzyme found only in plants. This enzyme is part of the biosynthesis 
pathway leading to the formation of branched chain amino acids. Animals 
lack ALS and this biosynthetic pathway. This lack of ALS contributes to 
the relatively low toxicity of sulfonylurea herbicides in animals. 
There is no reliable information that would indicate or suggest that 
triflusulfuron methyl has any toxic effects on mammals that would be 
cumulative with those of any other chemical.

E. Safety Determination

    1. U.S. population. Based on the completeness and reliability of 
the toxicology data base and using the conservative assumptions 
presented earlier, EPA has established a chronic RfD of 0.024 mg/kg/
day. This was based on the NOAEL for the 2-year chronic rat study (2.44 
mg/kg/day) and a 100-fold safety factor. It has been concluded that the 
aggregate exposure was 0.6% of the cRfD. Generally, exposures below 
100% of the cRfD are of no concern because it represents the level at 
or below which daily aggregrate exposure over a lifetime will not pose 
appreciable risk to human health. Thus, there is reasonable certainty 
that no harm will result from aggregate exposures to triflusulfuron 
methyl residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of triflusulfuron 
methyl, data from the previously discussed developmental and multi-
generation reproductive toxicity studies were considered.
    Developmental studies are designed to evaluate adverse effects on 
the developing organism resulting from pesticide exposure during 
prenatal development. Reproduction studies provide information relating 
to reproductive and other effects on adults and offspring from the 
prenatal and postnatal exposures to the pesticide. The studies with 
triflusulfuron methyl demonstrated no evidence of developmental 
toxicity at exposures below those causing maternal toxicity. This 
indicates that developing animals are not more sensitive to the effects 
of triflusulfuron methyl administration than adults.
    FFDCA section 408 provides that EPA may apply an additional 
uncertainty factor for infants and children in the case of threshold 
effects to account for prenatal and postnatal toxicity and the 
completeness of the data base. Based on current toxicological data 
requirements, the data base for triflusulfuron methyl relative to 
prenatal and postnatal effects for children is complete.
    In addition, the NOAEL of 2.44 mg/kg/day in the chronic rat study 
(and upon which the cRfD is based) is much lower than the NOAELs 
defined in the reproduction and developmental toxicology studies. The 
sub-population with the highest level of exposure was non-nursing 
infants, where exposure was < 1.8% of the cRfD. Based on these 
conservative analyses, there is reasonable certainty that no harm will 
result to infants and children from aggregate exposures to 
triflusulfuron methyl.

F. International Tolerances

    There are no Codex Maximum Residue Levels established for 
triflusulfuron methyl.

[FR Doc. 99-33159 Filed 12-21-99; 8:45 am]
BILLING CODE 6560-50-F