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Return to Fomesafen Index PageFomesafen (IR-4). September 17, 1997. Pesticide Tolerance Petition. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/1997/September/Day-17/p24692.htm
[Federal Register: September 17, 1997 (Volume 62, Number 180)]
[Notices]
[Page 48848-48856]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17se97-68]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-754; FRL-5735-8]
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 and/or amendment of regulations
for residues of certain pesticide chemicals in or on various food
commodities.
DATES: Comments, identified by the docket control number PF-754, must
be received on or before October 17, 1997.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7506C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 1132, 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: By mail: Sidney Jackson, Product
Manager (PM) 43, Minor Use, Inerts, Emergency Response Branch,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location and telephone number: Rm. 274, CM#2, 1921 Jefferson
Davis Highway, Arlington, VA., (703) 305-7610. e-mail:
jackson.sidney@epamail.epa.gov.
[[Page 48849]]
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 raw 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, as well as the public version,
has been established for this notice of filing under docket control
number PF-754 (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''.
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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket control number (insert docket number) and
appropriate petition number. Electronic comments on this notice may be
filed online at many Federal Depository Libraries.
Authority: 21 U.S.C. 346a.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: September 5, 1997.
James Jones,
Acting Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Below summaries of the pesticide petitions are printed. The
summaries of the petitions were prepared by the petitioners. 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.
3. Zeneca Ag Products
PP 6E4653
EPA has received a pesticide petition (PP 6E4653) from the
Interregional Research Project No. 4 (IR-4), New Jersey Agricultural
Experiment Station, P.O. Box 231, Rutgers University, New Brunswick, NJ
08903, 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 the herbicide sodium salt of
fomesafen (also referred to in this document as fomesafen, 5-[2-chloro-
4- (trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide, in or
on the raw agricultural commodity snap beans at 0.05 parts per million
(ppm).
A. Residue Chemistry
1. Plant metabolism. Fomesafen metabolism has been extensively
studied in soybeans. Once in the plant, fomesafen shows very rapid
metabolism with either cleavage or conjugation of the intermediate
degradation products to a complex mixture of low level degradation
products. There is no significant translocation. For purposes of
regulation, the parent compound fomesafen is the residue of concern on
harvested bean crops.
2. Analytical method. The method of analysis uses High Pressure
Liquid Chromatography. It is method GAM-RM-001/86, which was developed
for analytical work on soybeans and adapted for use on snap beans. The
limit of detection of the analytical method is 0.025 ppm.
3. Magnitude of residues. Residue data are available for fomesafen
applied post-emergence on snap beans at the maximum label rate of 0.375
pounds active ingredient/acre (lb ai/A). The residue field trials were
conducted by the IR-4 project in the States of Florida, North Carolina,
New York, Oregon, and Wisconsin, representing approximately 50% of the
national snap bean acreage. Each treated plot received a single post-
emergence, prebloom application at either 0.25 or 0.375 lb ai/A. Four
snap bean samples per treatment were collected from each trial. Samples
were harvested 22 to 31 days after treatment, a normal range for snap
beans. There are no detectable residues in snap beans when fomesafen is
applied up to 0.375 lb ai/A prior to pod development, pre-bloom
application.
Based on the results of the poultry and ruminant metabolism
studies, fomesafen is rapidly metabolized and excreted. There are no
expected residues of fomesafen in meat, milk, or eggs. Snap beans are
not a significant livestock feed commodity.
B. Toxicological Profile
1. Acute toxicity. The acute toxicity profile of technical
fomesafen is low by oral, dermal and inhalation routes. Similarly the
formulated fomesafen
[[Page 48855]]
product (REFLEX) is of low oral, dermal and inhalation toxicity but is
classed as Category I toxicity based on the highest hazard, severe eye
irritancy. Fomesafen is not a skin sensitizer and only a slight
irritant to the skin.
Results of the acute toxicity testing with REFLEX show acute oral
in the rat lethal dose (LD)50 > 2,000 milligram (mg)/
kilogram (kg), acute dermal in the rabbit LD50 > 2,000 mg/
kg, acute inhalation in the rat LD50 > 5.48 mg/liter (L),
eye irritation in the rabbit showed severe irritancy, and skin
irritation in the rabbit showed a slight irritancy. REFLEX is not a
skin sensitizer.
2. Genotoxicity. Fomesafen tested negative in assay systems for
gene mutation, structural chromosome aberration and other genotoxic
effects. However fomesafen did produce a weak clastogenic response in
the rat bone marrow when the analysis of the data was undertaken with
gap-type aberrations both included and excluded.
In the registrant's view, gap-type aberrations (small
discontinuities in the staining of the chromosomes, as distinct from
breaks), do not indicate significant chromosomal damage and should be
excluded from the evaluation of such assays. Their conclusion therefore
is that these data should be considered to indicate no clastogenic
effect of fomesafen with no biologically significant genotoxic effects.
3. Reproductive and developmental toxicity. In a 2-generation
reproduction study in rats fed diets containing 0, 50, 250 or 1,000 ppm
fomesafen (equivalent to 2.5, 12.5 or 50 mg/kg/day) no reproductive
effects were observed. The no observed effects level (NOEL) for
systemic toxicity (reduction in body weight gain and liver necrosis) is
established at 250 ppm for this study.
In a developmental toxicity study in rats given oral doses of
fomesafen at 0, 50, 100, or 200 mg/kg/day on gestation days 6 to 15
there was no developmental toxicity and the NOEL was established at 50
mg/kg/day, following evaluation of a second study at lower doses.
A developmental toxicity study in rabbits given oral doses of 0,
2.5, 10, or 40 mg/kg/day on gestation days 6 to 18 with no
developmental toxicity.
4. Subchronic toxicity. Subchronic oral toxicity studies in the rat
(90-day) and dog (26 weeks) show that the liver is the primary target
of toxicity in both sexes. Rats were dosed at 1, 5, 100, and 1,000 ppm
in the diet. The lowest observed effect level (LOEL) in this study was
100 ppm (5 mg/kg/day) and the NOEL was 5 ppm (0.25 mg/kg/day). The dogs
were dosed at 0.1, 1 and 25 mg/kg/day. The LOEL in this study was 25
mg/kg/day and the NOEL was 1 mg/kg/day.
A 21-day dermal toxicity study in the rabbit at doses of 10, 100,
and 1,000 mg/kg/day showed moderate to severe skin irritation at the
application site but no systemic effects at doses up to 1,000 mg/kg/
day. The LOEL for skin irritation was 100 mg/kg/day and the NOEL was 10
mg/kg/day.
5. Chronic toxicity. Beagle dogs were administered fomesafen in
gelatin capsules at dose levels of 0, 0.1, 1.0 or 25 mg/kg body weight
(bwt)/day for 26 weeks with a NOEL of 1.0 mg/kg/day. There were no
deaths, no clinical signs of toxicity and no treatment related effects
on bodyweight or food consumption. Evidence of toxicity was observed at
25 mg/kg/day. Hypolipidemia was present in dogs of both sexes. At
autopsy liver weight was increased at 25 mg/kg/day; microscopic
examination revealed eosinophilic damage and peroxisome proliferation
in both sexes.
A 2-year feeding/carcinogenicity study with rats fed diets
containing 0, 5, 100, or 1,000 ppm of fomesafen gave a NOEL for
systemic effects of 5 ppm (0.25 mg/kg/day). At the lowest-effect level
(LEL) 100 ppm (5 mg/kg/day) there were minor changes associated with
liver toxicity. There were no carcinogenic effects observed under the
conditions of the study.
A carcinogenicity study was conducted in CD-1 mice fed diets
containing 0, 1, 10, 100 or 1,000 ppm fomesafen (equivalent to 0.15,
1.5, 15 or 150 mg/kg/day) for up to 89 weeks. Increased mortality was
seen at 1,000 ppm in both males and females and liver weights were
increased at 100 and 1,000 ppm. A dose-related increase in the
incidence of benign and malignant hepatocellular tumors was observed.
Both tumor types were statistically significant in males and females at
1,000 ppm. At the 100 ppm feeding level (male and female), the
increased incidence was confined to benign tumors. The increase in
benign liver tumors at 1 ppm in males only was not considered related
to fomesafen, due to the lack of any increase at 10 ppm.
The Agency has classified fomesafen as a Group C carcinogen
(possible human carcinogen) with a potency factor (Q1*) of 0.0019 mg/
kg/day.
6. Animal metabolism. Fomesafen is well absorbed and completely
metabolized in the rat. Excretion is rapid with 90% of the compound
excreted within 7 days of ingestion. There is no accumulation of
fomesafen.
7. Metabolite toxicology. Toxicity testing results for the
fomesafen parent compound is indicative of any metabolites, either in
the plant or animal.
C. Aggregate Exposure
1. Dietary exposure. For purposes of assessing the potential
dietary exposure, ZENECA estimated aggregate exposure based on the
tolerance for fomesafen on soybeans and snap beans at 0.05 ppm. Dietary
exposure to residues of fomesafen in or on food will be limited to
residues on soybean and snap beans. Based on the animal metabolism
data, and because there are no residues on the crops at time of
harvest, the company has concluded that there is reasonable expectation
that no measurable residues of fomesafen will occur in meat, milk,
poultry, or eggs from this use. There are no other established U.S.
tolerances for fomesafen.
2. Food. On the bases of the Group C carcinogen classification of
fomesafen the upper-bound carcinogenic risk from dietary exposure to
fomesafen was calculated using a potency factor (Q*) of 0.19 (mg/kg/
day)-1 and dietary exposure as estimated by the Anticipated
Residue Contribution (ARC) for existing tolerances and the proposed
tolerance for snap beans. The upper-bound carcinogenic risk from
established tolerances and the proposed tolerance for snap beans is
calculated at 1.56 x 10-6 for the U.S. Population. The
upper-bound carcinogenic risk from the proposed use on snap beans is
calculated at 1.4 x 10-6. Therefore, the potential cancer
risk from residues of fomesafen resulting from the combined established
tolerance on soybeans and the proposed tolerance for snap beans is
negligible.
3. Drinking water. Other potential sources of exposure of the
general population to residues of pesticides are residues in drinking
water and exposure from non-occupational sources. Field dissipation
data and a prospective groundwater study indicate that fomesafen is
persistent and has the potential to leach to groundwater. There is no
established Maximum Concentration Level (MCL) for residues in drinking
water. No drinking water health advisory has been established.
Risk of contaminating surface water. Zeneca contends that fomesafen
is unlikely to enter surface water bodies to any significant degree
except by direct accidental over-spray. Should this arise, fomesafen
will be readily degraded by a number of contributory processes.
Fomesafen is not persistent in water in sunlit aquatic conditions. All
these processes will ensure that any fomesafen entering surface water
bodies will be short-lived and will not result in
[[Page 48856]]
any significant contamination of potential drinking water sources.
Therefore, Zeneca concludes that potential exposures from residues
of fomesafen in drinking water added to the current dietary exposure
will not present significant risk to the U.S. population.
4. Non-dietary exposure. Since fomesafen is not registered for
residential or turf uses, exposures from other than dietary or
occupational sources are extremely unlikely. At this time there are no
reliable data to assess the potential risk from non-dietary sources.
D. Cumulative Effects
Fomesafen is a diphenyl ether class of chemicals. At this time, EPA
has not made a determination that fomesafen and other compounds have a
common mechanism of toxicity resulting in cumulative effects.
Therefore, aggregate exposure is evaluated on the uses of fomesafen
only.
E. Safety Determination
1. U.S. population. The Reference Dose (RfD) for fomesafen has not
been established by the Agency's. For purposes of this action, the RfD
is calculated at 0.0025 mg/kg of body weight/day. The RfD is based on a
NOEL of 0.25 mg/kg/day from the rat feeding/carcinogenicity study and
an uncertainty factor of 100. The ARC for the overall U.S. population
from established tolerances and the proposed tolerance for snap beans
utilizes 1.4% of the RfD. EPA generally has no concern for exposures
below 100% of the RfD.
The upper-bound carcinogenic risk from established tolerance on
soybeans and the proposed tolerance for snap beans is calculated at
1.56 x 10-6 for the U.S. population, based on the available
market share data. The upper-bound carcinogenic risk from the proposed
use on snap beans is calculated at 1.4 x 10-6. Therefore,
Zeneca believes that the potential cancer risk from residues of
fomesafen resulting from the combined established tolerance on soybeans
and the proposed tolerance for snap beans is negligible.
2. Infants and children. Zeneca noted that the potential for
additional sensitivity for infants and children to residues of
fomesafen have been considered based on the three-generation
reproductive study in rats and the developmental toxicity studies in
rat and rabbit. Zeneca concluded that fomesafen showed no evidence of
reproductive toxicity and caused no developmental toxicity in the
rabbit or in the rat.
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 for fomesafen. Zeneca AG Products concludes that there is
reasonable certainty that no harm will result to infants and children
from aggregate exposure to fomesafen.
F. International Tolerances
There are no Codex Maximum Residue Levels established for fomesafen
residues.
[FR Doc. 97-24692 Filed 9-16-97; 8:45 am]
BILLING CODE 6560-50-F