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Carfentrazone-ethyl (FMC). January 30, 1998. Pesticide Tolerance Petition. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/1998/January/Day-30/p2363.htm
[Federal Register: January 30, 1998 (Volume 63, Number 20)]
[Notices]
[Page 4631-4640]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30ja98-55]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-788; FRL-5766-2]
Notice of Filing of Pesticide Petitions
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 the docket control number PF-788, must
be received on or before March 2, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7502C), Information Resources and Services
Division, 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 to: opp-
docket@epamail.epa.gov. Follow 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. 119 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:
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Office location/
Product Manager telephone number Address
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Joanne Miller (PM 23)......... Rm. 237, CM #2, 703- 1921 Jefferson
305-6224, e-mail: Davis Hwy,
miller.joannes@epamai Arlington, VA
l.epa.gov.
Cynthia Giles-Parker (PM 22).. Rm. 229, CM #2, 703- Do.
305-7740, e-mail:
giles-
parker.cynthia@epamai
l.epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions 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 these petitions
contain 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-788] (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:
opp-docket@epamail.epa.gov
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 5.1/6.1 or ASCII file
format. All comments and data in electronic form must be identified by
[[Page 4632]]
the docket control number [PF-788] and appropriate petition number.
Electronic comments on this notice 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
requirements.
Dated: January 22, 1998.
James Jones,
Acting 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
PP 7F4795
EPA has received a pesticide petition (PP 7F4795) 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 establishing a tolerance
for residues of carfentrazone-ethyl in or on the raw agricultural
commodities (RAC) cereal grain at 0.1 parts per million (ppm), 0.3 ppm
in or on hay; 0.2 ppm in or on straw; 1.0 ppm in or on forage; 0.15 ppm
in or on stover and 0.1 ppm in or on sweet corn, K + CWHR (kernels plus
cob with husk removed) and in or on the RACs soybeans and soybean seed
at 0.1 ppm. EPA has determined that the petition contains data or
information regarding the elements set forth in section 408(d)(2) of
the FFDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
petition.
A. Residue Chemistry
1. Plant metabolism. The metabolism of carfentrazone-ethyl in
plants is adequately understood. Corn, wheat, and soybean 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 (LOQ) 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, 24 corn trials, and 22 soybean trials
in the appropriate EPA regions. The RACs 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; and 0.1 ppm for soybean seed. 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
neuropathology.
2. Genotoxicity. 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 No observed effect level (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 highest dose tested 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. Ninety-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 (1,178.3 mg/kg/day for males; 1,433.5 mg/kg/day for females)
which was the highest dose tested.
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.
[[Page 4633]]
An 18 Month Oncogenicity study in the mouse had a carcinogenic NOEL
that was greater than 7,000 ppm (>1,090 mg/kg/day for males; >1,296 mg/
kg/day for females) based on no evidence of carcinogenicity at the
highest dose tested. 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. The doses tested are adequate for identifying
a cancer risk. Thus, a cancer risk assessment is not necessary.
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
1. 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: September 30, 1997, 62 FR 51032-51038). Thus an acute dietary
risk assessment is not necessary.
ii. Chronic dietary. Based on the available toxicity data, the EPA
has established a provisional Reference Dose (RfD) for carfentrazone-
ethyl of 0.06 mg/kg/day. The RfD for carfentrazone-ethyl is based on a
90-day feeding study in rats with a threshold NOEL of 57.9 mg/kg/day
and an uncertainty factor of 100, with an additional modifying factor
of 10 to account for the fact that the chronic studies have not yet
been reviewed by the EPA. For purposes of assessing the potential
chronic dietary exposure, a Tier 1 dietary risk assessment was
conducted based on the Theoretical Maximum Residue Contribution (TMRC)
from the proposed tolerances for carfentrazone-ethyl on soybeans at 0.1
ppm, wheat at 0.2 ppm and corn (field) at 0.15 ppm. (The TMRC is a
``worse case'' estimate of dietary exposure since it is assumed that
100% of all crops for which tolerances are established are treated and
that pesticide residues are present at the tolerance levels.) At this
time the dietary exposure to residues of carfentrazone-ethyl in or on
food will be limited to residues on soybeans, wheat and corn. There are
no other established U.S. tolerances for carfentrazone-ethyl, and there
are no registered uses for carfentrazone-ethyl on food or feed crops in
the U.S. In conducting this exposure assessment, the following very
conservative assumptions were made--100% of soybeans, wheat and corn
will contain carfentrazone-ethyl residues and those residues would be
at the level of the tolerance which result in an overestimate of human
exposure.
2. Food. Dietary exposure from the proposed uses would account for
1.3% or less of the RfD in subpopulations (including infants and
children).
3. Drinking water. Studies have indicated that carfentrazone-ethyl
will not move into groundwater, therefore water has not been included
in the dietary risk assessment.
4. 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
carfentrazone-ethyl.
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 U.S. 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 highest dose tested 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 reversible.
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 highest dose tested.
FFDCA section 408 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
[[Page 4634]]
appropriate for assessing aggregate risk to infants and children.
3. Reference dose (RfD). 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.
F. 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
acid. (PM 23)
[FR Doc. 98-2363 Filed 1-29-98; 8:45 am]
BILLING CODE 6560-50-F