carfentrazone-ethyl Pesticide Tolerance Petition Filing 5/98
[Federal Register: June 10, 1998 (Volume 63, Number 111)]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
FMC Corporation; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by the docket control number PF-810, must
be received on or before July 10, 1998.
ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Divison (7502C),
Office of Pesticides Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119,
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically by following
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential
business information should be submitted through e-mail.
Information submitted as a comment concerning this document may be
claimed confidential by marking any
part or all of that information as ``Confidential Business
Information'' (CBI). CBI should not be submitted through e-mail.
Information marked as CBI will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. A copy of the comment that
does not contain CBI must be submitted for inclusion in the public
record. Information not marked confidential may be disclosed publicly
by EPA without prior notice. All written comments will be available for
public inspection in Rm. 1132 at the address given above, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: Joanne Miller, Registration Support
Branch, Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW, Washington, DC 20460.
Office location, telephone number, and e-mail address: Rm. 237, Crystal
Mall CM #2, 1900 Jefferson Davis Highway, Arlington, VA 22202, (703)
305-6224; e-mail: firstname.lastname@example.org.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemical in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition
contains data or information regarding the elements set forth in
section 408(d)(2); however, EPA has not fully evaluated the sufficiency
of the submitted data at this time or whether the data supports
granting of the petition. Additional data may be needed before EPA
rules on the petition.
The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-810] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
``ADDRESSES'' at the beginning of this document.
Electronic comments can be sent directly to EPA at:
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number FRL-5793-1 and appropriate petition
number. Electronic comments on this proposed rule may be filed online
at many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
Dated: May 26, 1998.
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them 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. FMC Corporation
EPA has received a pesticide petition (PP 6G4615) from FMC
Corporation, 1735 Market Street, Philadelphia, PA 19103, proposing
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act,
21 U.S.C. 346a(d), to amend 40 CFR part 180 by extending a temporary
tolerance for the combined residue of the herbicide carfentrazone-ethyl
oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzene-propanoate) and its major
wheat metabolites: carfentrazone-ethyl chloropropionic acid (alpha, 2-
triazol-1-yl]-4-fluorobenzenepropanoic acid), 3-hydroxymethyl-F8426-
chloropropionic acid (alpha,2-dichloro-5-[4-difluoromethyl)-4,5-
fluorobenzenepropanoic acid), and 3-desmethyl-F8426 chloropropionic
acid (alpha, 2-dichloro-5-[4-difluoromethyl)-4,5-dihydro-5-oxo-1H-
1,2,4-triazol-l-yl]-4-fluorobenzenepropanoic acid) in or on wheat raw
agricultural commodities: 0.2 ppm in or on wheat hay, 0.2 ppm in or on
wheat straw, 0.2 ppm in or on wheat grain; and extending tolerance for
combined residue of the herbicide carfentrazone-ethyl (ethyl-alpha-2-
triazol-1-yl]-4-fluorobenzene-propanoate) and its major corn
metabolites: carfentrazone-ethyl chloropropionic acid (alpha, 2-
triazol-l-yl]-4-fluorobenzenepropanoic acid),and 3-desmethyl-F8426
chloropropionic acid (alpha, 2-dichloro-5-[4-difluoromethyl)-4,5-
dihydro-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoic acid) in
or on corn raw agricultural commodities: 0.15 ppm in or on corn forage,
0.15 ppm in or on corn fodder, 0.15 ppm in or on corn grain.
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
A. Residue Chemistry
1. Plant metabolism. The metabolism of carfentrazone-ethyl in
plants is adequately understood. Corn and wheat metabolism studies with
carfentrazone-ethyl have shown uptake of material into plant tissue
with no significant movement into grain or seeds. All three plants
extensively metabolized carfentrazone-ethyl and exhibited a similar
metabolic pathway. The residues of concern are the combined residues of
carfentrazone-ethyl and carfentrazone-ethyl- chloropropionic acid.
2. Analytical method There is a practical analytical method for
detecting and measuring levels of carfentrazone and its metabolites in
or on food with a limit of quantitation that allows monitoring of food
with residues at or above the levels set in the tolerances. The
analytical method for carfentrazone-ethyl involves separate analyses
for parent and its metabolites. The parent is analyzed by GC/ECD. The
metabolites are derivatized with boron trifluoride and acetic anhydride
for analysis by GC/MSD using selective ion monitoring.
3. Magnitude of residues. Carfentrazone-ethyl 50DF was applied
postemergent to 28 wheat trials, and 24 corn trials in the appropriate
EPA regions. The RAC's were harvested at
the appropriate growth stages and subsequent analyses determined that
the residues of carfentrazone-ethyl and its metabolites will not exceed
the proposed tolerances of 1.0, 0.3, 0.2 and 0.1 ppm for wheat forage,
hay, straw and grain, respectively; 0.1 ppm each for corn forage,
fodder, and grain. Residue data from a cow feeding study demonstrated
that no accumulation of carfentrazone-ethyl or its metabolites occurred
in milk or tissues.
B. Toxicological Profile
1. Acute toxicity. Carfentrazone-ethyl demonstrates low oral,
dermal and inhalation toxicity. The acute oral LD<INF>50</INF> value in
the rat was greater than 5,000 milligram/Kilograms (mg/kg), the acute
dermal LD<INF>50</INF> value in the rat was greater than 4,000 mg/kg
and the acute inhalation LC<INF>50</INF> value in the rat was greater
than 5.09 mg/L/4h. Carfentrazone-ethyl is non-irritating to rabbit skin
and minimally irritating to rabbit eyes. It did not cause skin
sensitization in guinea pigs. An acute neurotoxicity study in the rat
had a systemic no-observed-adverse-effect level (NOAEL) of 500 mg/kg
based on clinical signs and decreased motor activity levels; the NOAEL
for neurotoxicity was greater than 2,000 mg/kg highest dose tested
(HDT) based on the lack of neurotoxic clinical signs or effects on
2. Genotoxicty. Carfentrazone-ethyl did not cause mutations in the
Ames assay with or without metabolic activation. There was a positive
response in the Chromosome Aberration assay without activation but a
negative response with activation. The Mouse Micronucleus assay (an in
vivo test which also measures chromosome damage), the CHO/HGPRT forward
mutation assay and the Unscheduled DNA Synthesis assay were negative.
The overwhelming weight of the evidence supports the conclusion that
Carfentrazone-ethyl is not genotoxic.
3. Reproductive and developmental toxicity. Carfentrazone-ethyl is
not considered to be a reproductive or a developmental toxin. In the 2-
generation reproduction study, the NOEL for reproductive toxicity was
greater than 4,000 ppm (greater than 323 to greater than 409 mg/kg/
day). In the developmental toxicity studies, the rat and rabbit
maternal NOELs were 100 mg/kg/day and 150 mg/kg/day, respectively. The
developmental NOEL for the rabbit was greater than 300 mg/kg/day which
was the HDT and for the rat the NOEL was 600 mg/kg/day based on
increased litter incidences of thickened and wavy ribs at 1,250 mg/kg/
day. These two findings (thickened and wavy ribs) are not considered
adverse effects of treatment but related delays in rib development
which are generally believed to be reversible.
4. Subchronic toxicity 90-day feeding studies were conducted in
mice, rats and dogs with carfentrazone-ethyl. The NOEL for the mouse
study was 4,000 ppm (571 mg/kg/day), for the rat study was 1,000 ppm
(57.9 mg/kg/day for males; 72.4 mg/kg/day for females) and for dogs was
150 mg/kg/day. A 90-day subchronic neurotoxicity study in the rat had a
systemic NOEL of 1,000 ppm (59.0 mg/kg/day for males; 70.7 mg/kg/day
for females) based on decreases in body weights, body weight gains and
food consumption at 10,000 ppm; the neurotoxicity NOEL was greater than
20,000 ppm (1178.3 mg/kg/day for males; 1433.5 mg/kg/day for females)
which was the HDT.
5. Chronic toxicity. Carfentrazone-ethyl is not carcinogenic to
rats or mice. A 2-year combined chronic toxicity/oncogenicity study in
the rat was negative for carcinogenicity and had a chronic toxicity
NOEL of 200 ppm (9 mg/kg/day) for males and 50 ppm (3 mg/kg/day) for
females based on red fluorescent granules consistent with porphyrin
deposits in the liver at the 500 and 200 ppm levels, respectively. An
18-month oncogenicity study in the mouse had a carcinogenic NOEL that
was greater than 7,000 ppm (>1090 mg/kg/day for males; >1296 mg/kg/day
for females) based on no evidence of carcinogenicity at the HDT. A 1-
year oral toxicity study in the dog had a NOEL of 50 mg/kg/day based on
isolated increases in urine porphyrins in the 150 mg/kg/day group (this
finding was not considered adverse).
Using the Guidelines for Carcinogen Risk Assessment, carfentrazone-
ethyl should be classified as Group ``E'' for carcinogenicity -- no
evidence of carcinogenicity -- based on the results of carcinogenicity
studies in two species. There was no evidence of carcinogenicity in an
18-month feeding study in mice and a 2-year feeding study in rats at
the dosage levels tested (DLT). The doses tested are adequate for
identifying a cancer risk. Thus, a cancer risk assessment is not
6. Animal metabolism. The metabolism of carfentrazone-ethyl in
animals is adequately understood. Carfentrazone-ethyl was extensively
metabolized and readily eliminated following oral administration to
rats, goats, and poultry via excreta. All three animals exhibited a
similar metabolic pathway. As in plants, the parent chemical was
metabolized by hydrolytic mechanisms to predominantly form
carfentrazone-ethyl-chloropropionic acid which was readily excreted.
7. Endocrine disruption. An evaluation of the potential effects on
the endocrine systems of mammals has not been determined; however, no
evidence of such effects were reported in the chronic or reproductive
toxicology studies described above. There was no observed pathology of
the endocrine organs in these studies. There is no evidence at this
time that carfentrazone-ethyl causes endocrine effects.
C. Aggregate Exposure
Dietary exposure--i. Acute dietary. The Agency has determine that
there is no concern for an acute dietary risk assessment since the
available data do not indicate any evidence of significant toxicity
from a 1-day or single event exposure by the oral route Federal
Register of September 30, 1997 (62, FR 189). Thus an acute dietary risk
assessment is not necessary.
ii. Food. Dietary exposure from the proposed uses would account for
1.3% or less of the RfD in subpopulations (including infants and
iii. Drinking water. Studies have indicated that carfentrazone-
ethyl will not move into groundwater, therefore water has not been
included in the dietary risk assessment.
iv. Non-dietary exposure. No specific worker exposure tests have
been conducted with carfentrazone-ethyl. The potential for non-
occupational exposure to the general population has not been fully
assessed. No specific worker exposure tests have been conducted with
D. Cumulative Effects
EPA is also required to consider the potential for cumulative
effects of carfentrazone-ethyl and other substances that have a common
mechanism of toxicity. EPA consideration of a common mechanism of
toxicity is not appropriate at this time since EPA does not have
information to indicate that toxic effects produced by carfentrazone-
ethyl would be cumulative with those of any other chemical compounds;
thus only the potential risks of carfentrazone-ethyl are considered in
this exposure assessment.
E. Safety Determination
1. U.S. population. Using the conservative exposure assumptions
described and based on the completeness and reliability of the toxicity
data, the aggregate exposure to carfentrazone-ethyl will utilize 0.61%
of the RfD for the US population. EPA generally has no concern for
exposures below 100% of the RfD. Therefore,
based on the completeness and reliability of the toxicity data and the
conservative exposure assessment, there is a reasonable certainty that
no harm will result from aggregate exposure to residues of
carfentrazone-ethyl, including all anticipated dietary exposure and all
other non-occupational exposures.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of carfentrazone-ethyl,
EPA considers data from developmental toxicity studies in the rat and
rabbit and the 2-generation reproduction study in the rat. The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism resulting from pesticide exposure during
prenatal development. Reproduction studies provide information relating
to effects on the reproductive capacity of males and females exposed to
the pesticide. Developmental toxicity was not observed in developmental
toxicity studies using rats and rabbits. In these studies, the rat and
rabbit maternal NOELs were 100 mg/kg/day and 150 mg/kg/day,
respectively. The developmental NOEL for the rabbit was greater than
300 mg/kg/day which was the HDT and for the rat was 600 mg/kg/day based
on increased litter incidences of thickened and wavy ribs. These two
findings are not considered adverse effects of treatment but related
delays in rib development which are generally believed to be
In a 2-generation reproduction study in rats, no reproductive
toxicity was observed under the conditions of the study at 4,000 ppm
which was the HDT.
Section 408 of the FFDCA provides that EPA may apply an additional
safety factor for infants and children in the case of threshold effects
to account for pre- and post-natal toxicity and the completeness of the
database. Based on the current toxicological data requirements, the
database relative to pre- and post-natal effects for children is
complete and an additional uncertainty factor is not warranted.
Therefore at this time, the provisional RfD of 0.06 mg/kg/day is
appropriate for assessing aggregate risk to infants and children.
F. Reference Dose
Using the conservative exposure assumptions described above, the
percent of the RfD that will be utilized by aggregate exposure to
residues of carfentrazone-ethyl for non-nursing infants (<1-year old)
would be 0.28% and for children 1-6 years of age would be 1.37% (the
most highly exposed group). Based on the completeness and reliability
of the toxicity data and the conservative exposure assessment, there is
a reasonable certainty that no harm will result to infants and children
from aggregate exposure to the residues of carfentrazone-ethyl
including all anticipated dietary exposure.
G. International Tolerances
There are no Codex Alimentarius Commission (Codex) Maximum Residue
Levels (MRLs) for carfentrazone-ethyl on any crops at this time.
However, MRLs for small grains in Europe have been proposed which
consist of carfentrazone-ethyl and carfentrazone-ethyl-chloropropionic
[FR Doc. 98-15177 Filed 6-9-98; 8:45 am]
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