[Federal Register Volume 64, Number 32 (Thursday, February 18, 1999)]
[Notices]
[Pages 8087-8090]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-4025]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-838; FRL-6036-4]
FMC Corporation; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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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-838, must
be received on or before March 22, 1999.
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. 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: James A. Tompkins, 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. 239, Crystal Mall
#2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-5697
e-mail: [email protected].
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-838] (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
[[Page 8088]]
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:
[email protected]
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 file format or
ASCII file format. All comments and data in electronic form must be
identified by the docket control number (PF-838) 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: February 10, 1999.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the views of the
petitioner. 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.
FMC Corporation
PP 7F4896
EPA has received a pesticide petition (PP 7F4896) 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 clomazone in or on the raw agricultural commodities
rice grain and rice straw 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. The metabolism of clomazone in plants is
adequately understood. The metabolism of clomazone has been studied in
both monocotyledonous and dicotyledonous plant species, such as corn
and soybeans. The residue of significance is the parent compound,
clomazone. This picture is consistent with plant metabolism studies in
other species (cotton, sweet potatoes, and tobacco), all of which have
shown a similar metabolic pathway with the residue of significance
being clomazone.
2. Analytical method. There is a practical analytical method for
detecting and measuring levels of clomazone in or on rice grain, straw,
and rice processed parts with a limit of detection that allows
monitoring of food for residues at or above the levels proposed in this
tolerance. Rice samples are analyzed using gas chromatography - mass
selective detection with a limit of quantification of 0.02 ppm, for
both straw and grain. Processed rice samples are analyzed using gas
chromatography - nitrogen-phosphorous detector with a limit of
quantification of 0.05 ppm.
3. Magnitude of residues. FMC conducted a residue study (consisting
of 18 trials) to determine the magnitude of the residue of clomazone
in/on rice grain and straw after treatment with one application of
Command 3ME at 0.6 lb. ai/A at pre-plant, pre-emergent, or early post
emergent. No detectable residues (detection limit = 0.01 ppm) of
clomazone were found in rice grain or straw in any sample, irrespective
of location or application method. A second study was conducted, using
an excess rate of 1.25 lb. ai/A applied as a pre-emergent treatment, to
determine the magnitude of the residue of clomazone in/on rice grain
and the extent of concentration into its processed fractions. No
detectable residues (detection limit = 0.01 ppm, limit of quantitation
(LOQ) = 0.05 ppm) of clomazone were found in rice grain or any of the
processed parts analyzed (polished rice, hulls or bran). Since no
detectable residues were found in any rice raw agricultural or
processed feed/feedstuff commodities from the field studies, animal
feeding studies in cow and poultry are not needed.
B. Toxicological Profile
1. Acute toxicity. The following mammalian toxicity studies have
been conducted with clomazone technical (unless noted otherwise) to
support registrations and/or tolerances of clomazone.
i. A rat acute oral study with an LD50 of 2,077
milligram kilogram (mg/kg) (male) and 1,369 mg/kg (female).
ii. A rabbit acute dermal LD50 of > 2,000 mg/kg.
iii. A rat acute inhalation LC50 of 6.25 mg/L (male),
4.23 mg/L (female) and 4.85 mg/L (combined sexes).
iv. A primary eye irritation study in the rabbit which showed
practically no irritation.
v. A primary dermal irritation study in the rabbit which showed
minimal irritation.
vi. A primary dermal sensitization study in the guinea pig which
showed no sensitization.
Acute delayed neurotoxicity - clomazone, and its known metabolites,
are not structurally related to known neurotoxic substances.
2. Genotoxicty. The following genotoxicity tests were all negative:
Ames Assay; CHO/HGPRT Mutation Assay; and Structural Chromosomal
Aberration. The Unscheduled DNA Synthesis genotoxicity was negative
with activation; weakly positive without activation.
3. Reproductive and developmental toxicity. A 2-generation
reproduction study was conducted in the rat with a parental systemic no
observed adverse effect level (NOAEL) of 1,000 ppm (50 milligram
kilogram day (mg/kg/day) based on decreased body weight (bwt) and food
consumption at 2,000 ppm; and a progeny systemic NOAEL of 1,000 ppm (50
mg/kg/day) based on decreased pup bwt at 2,000 ppm. The reproductive
performance NOAEL was > 4,000 ppm which was the highest dose tested
(HDT). There was an unexplained decrease in the fertility index during
mating of the F1b generation at 4,000 ppm which was not observed in the
F1a litter or repeated in the F2 generation. Additionally, there was
one F2a pup at 1,000 ppm which had non-functional hindlimbs and one F2b
pup at 4,000 ppm which had extended hindlimbs with no flexion at the
ankle. These limb abnormalities were not considered treatment-related
for the following reasons, i) there was no dose response observed, ii)
the findings were not statistically significant, iii) the findings were
not repeated at the 1,000 ppm dose level in the F2b litter or found in
the F1a or F1b litters, and iv) these findings or related hindlimb
abnormalities were
[[Page 8089]]
not observed in developmental studies at gavage dose levels up to 100
mg/kg/day in the rat or 240 mg/kg/day in the rabbit.
A developmental toxicity study in rats given gavage doses of 100,
300 and 600 mg/kg/day and with maternal and fetal NOAELs of 100 mg/kg/
day. The maternal NOAEL is based on decreased locomotion, genital
staining and runny eyes and the developmental NOAEL is based on
increased incidence of delayed ossification at 300 mg/kg/day. This
study was negative for teratogenicity at all doses tested.
A developmental toxictiy study in rabbits given gavage doses of 30,
240 and 700 mg/kg/day with maternal and fetal NOAELs of 240 mg/kg/day.
The maternal NOAEL is based on a decrease in bwt and the developmental
NOAEL is based on an increase in the number of fetal resorptions at 700
mg/kg/day. This study was negative for teratogenicity at all doses
tested.
In all cases, the reproductive and developmental NOAELs were equal
to the parental NOAELs, thus indicating that clomazone does not pose
any increased risk to infants or children.
4. Subchronic toxicity. In a 90 day feeding subchronic study in
mice the NOAEL was 20 ppm (<2.9 mg/kg/day) based on liver cytomegaly at
20 ppm.
5. Chronic toxicity. A 12 month feeding study in the dog with a
NOAEL of 500 ppm (14.0 mg/kg/day for males; 14.9 mg/kg/day for females)
based on increased blood cholesterol and liver weights at 2,500 ppm.
A 24 month chronic feeding/oncogenicity study in the rat with a
NOAEL of 100 ppm (4.3 mg/kg/day for males; 5.5 mg/kg/day for females)
based on increased liver weights and increased liver cytomegaly at 500
ppm. There were no oncogenic effects observed under the conditions of
the study.
A 24 month chronic feeding/oncogenicity study in the mouse with a
NOAEL of 100 ppm (15 mg/kg/day) based on an increase in the white blood
cell count. There were no oncogenic effects observed under the
conditions of the study.
Using the Guidelines for Carcinogen Risk Assessment, it is proposed
that clomazone be classified as Group E for carcinogenicity (no
evidence of carcinogenicity) based on the results of carcinogenicity
studies in two species. In 24 month feeding/oncogenicity studies in
rats and mice at dosages up to 2,000 ppm, there was no evidence of
caricnogenicity. The NOAEL in the 24 month feeding/oncogenicity study
in the rat was 100 ppm (4.3 mg/kg/day for males and 5.5 mg/kg/day for
females). The NOAEL in the 24 month feeding/oncogenicity study in mice
was 100 ppm (15 mg/kg/day). The studies were negative for carcinogenic
effects at all dosage levels tested.
The reference dose (RfD) for clomazone has been established at
0.043 mg/kg/day. The RfD for clomazone is based on the 24 month
feeding/carcinogenicity study in the rat with a NOAEL of 4.3 mg/kg/day
and an uncertainty factor of 100.
6. Animal metabolism. The metabolism of clomazone in animals is
adequately understood. Clomazone degrades rapidly and extensively in
rats, goats and poultry to a variety of metabolites which were readily
excreted from the body via excreta.
7. Metabolite toxicology. No clomazone related metabolite residues
have been identified as being of toxicological concern. The residue of
significance is parent. Clomazone, has been thoroughly investigated in
a full battery of studies including acute, genetic, reproduction
developmental and oncogenic tests. These studies have demonstrated that
clomazone has low acute toxicity, an overall absence of genotoxicity
and does not cause reproductive toxicity, developmental toxicity or
carcinogenicity.
8. Endocrine disruption. No specific tests have been conducted with
clomazone to determine whether the herbicide may have an effect in
humans that is similar to an effect produced by a naturally occurring
estrogen or other endocrine effects. It should be noted, however, that
the chemistry of clomazone is unrelated to that of any compound
previously identified as having estrogen or other endocrine effects.
Additionally, a standard battery of required studies has been
completed. These studies 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. No
endocrine effects were noted in any of these studies with clomazone.
C. Aggregate Exposure
1. Dietary exposure--Food. For purposes of assessing the potential
dietary exposure, EPA has estimated aggregate exposure based on the
Theoretical Maximum Residue Contribution (TMRC) from the established
tolerances for clomazone. The TMRC is a ``worst 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. Dietary exposure to residues of
clomazone in or on food will be limited to residues on cabbage (0.1
ppm), cottonseed (0.05 ppm), cucumber (0.1 ppm), succulent peas (0.05
ppm), peppers (0.05 ppm), pumpkins (0.1 ppm), soybeans (0.05 ppm),
winter squash (0.1 ppm), summer squash (0.1 ppm), sweet potato (0.05
ppm), snap beans (0.05 ppm) and rice (0.05 ppm). Various feedstuffs
from cotton and soybeans are fed to animals, thus exposure of humans to
residues might result if such residues carry through to meat, milk,
poultry or eggs. No tolerances are proposed for meat, milk, poultry or
egg since no detectable residues from clomazone have been found in the
past or were found in any rice raw agricultural commodity or processed
animal feed products. As noted above, in conducting this exposure
assessment, EPA has made very conservative assumptions, i.e., 100% of
crops treated will contain clomazone residues and those residues would
be at the level of the tolerance. It is FMC's opinion that these
assumptions result in an overestimate of human exposure.
2. Drinking water. It is unlikely that there will be exposure to
residues of clomazone through drinking water supplies. A field mobility
study was conducted at a loamy sand location. Clomazone was found only
in the top 0-1 ft. soil samples during the 61 day study period. No
clomazone residue (<0.02 ppm) was detected in the deeper soil levels
(1-2, 2-3 and 3-4 ft.). Mathematical modeling (PESTANS) was also
applied to the loamy sand site. PESTANS showed very limited potential
for movement of clomazone. That is, clomazone did not move lower than
the top seven inches of soil over the first 30 days with 10 inches of
precipitation and 100% recharge. Predictions were also obtained for
other soil types including sand, sandy loam, silt loam and clay loam.
These outputs yielded a similar conclusion, that clomazone has low
potential for downward movement with its highest mobility being sand.
The field leaching study and PESTANS modeling results were further
confirmed by field dissipation studies conducted in silt loam (IL and
AR), sandy loam (NJ), sandy clay loam (NC), silty clay loam (IA) and
silt loam (LA) soils. Results of these studies demonstrated that
clomazone tended to remain in the top soil layer (0-6''), with residues
in the 6-12'' layer being at or below method sensitivity (0.10 ppm) and
generally declining to non-detectable. An aquatic field dissipation
study conducted at locations in AR and TX, having silty
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clay loam and loam soils characteristics respectively. Soil samples
were taken over a period of 12 months following the herbicide
application. Detectable residues of clomazone were found only in the 0-
6'' horizon. Should movement into surface water occur, potential for
clomazone residues to be detected in drinking water supplies at
significant levels is minimal. Results from an aquatic field
dissipation study (static water situation) demonstrated half-lives of
12-13 days, indicating even shorter durations are likely under flowing
water situations. Accordingly, there is no reasonable expectation that
there would be an additional incremental aggregate dietary contribution
of clomazone through groundwater or surface water.
3. Non-dietary exposure. Clomazone is only registered for use on
food crops. Since the proposed use on rice is consistent with existing
registrations, there will be no non-dietary, non-occupational exposure.
D. Cumulative Effects
Clomazone is an isoxazolidinone herbicide. No other registered
chemical exists in this class of chemistry. Therefore, given
clomazone's unique chemistry low acute toxicity, the absence of
genotoxic, oncogenic, developmental or reproductive effects, and low
exposure potential (see sections A and C), the expression of cumulative
human health effects with clomazone and other natural or synthetic
pesticides is not anticipated.
E. Safety Determination
1. U.S. population. Using the conservative exposure assumptions
described above, based on the completeness and reliability of the
toxicology data, it is concluded that aggregate exposure due to
existing registered uses of clomazone will utilize less than one of the
RfD for the U.S. population. Additionally, an analysis concluded that
aggregate exposure to clomazone adding rice at a 0.05 ppm tolerance
level will utilize 0.17% of the RfD for the U.S. population. EPA
generally has no concern for exposures below 100% of the RfD because
the RfD represents the level at or below which daily aggregate dietary
exposure over a lifetime will not pose appreciable risks to human
health. It is concluded that there is a reasonable certainty that no
harm will result from aggregate exposure to residues of clomazone,
including all anticipated dietary exposure.
2. Infants and children. Based on the current toxicological data
requirements, the database relative to pre- and post-natal effects for
children is complete (See section B.3). Further, for clomazone, the
NOAEL in the 2 year feeding study which was used to calculate the RfD
(0.043 mg/kg/day) is already lower than the NOAELs from the
reproductive and developmental studies by a factor of more than 10-
fold. Therefore, it can be concluded that no additional uncertainty
factors are warranted and that the RfD at 0.043 mg/kg/day is
appropriate for assessing aggregate risk to infants, children as well
as adults.
Using the conservative exposure assumptions described above, FMC
has concluded that the percent of the RfD that will be utilized by
aggregate exposure to residues of clomazone in/on rice for non-nursing
infants (< 1 year old), the population subgroup most sensitive, is 0.15
and the percent of the RfD that will be utilized by the children (1-6
years old) population subgroup is 0.037. The percent of the RfD
utilized for infants and children for rice plus all other current
clomazone tolerances is 0.640 and 0.286 respectively.
Based on the above information, FMC has concluded that there is a
reasonable certainty that no harm will result to infants, children or
adults from dietary food consumption exposure to clomazone residues
from either rice foods alone or rice foods plus all other clomazone
treated human dietary food sources.
F. International Tolerances
There are Codex residue limits for residues of clomazone in or on
cottonseed, oilseed, peas, potatoes, rape, rice, soybeans, sugarcane,
and tobacco.
[FR Doc. 99-4025 Filed 2-17-99; 8:45 am]
BILLING CODE 6560-50-F