[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