Notice of Filing a Pesticide Petition to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food
[Federal Register: March 29, 2000 (Volume 65, Number 61)]
[Notices]
[Page 16602-16608]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29mr00-67]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-924; FRL-6495-5]
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-924, must be
received on or before April 28, 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-924 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Shaja R. Brothers,
Registration Support Branch, Registration Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg.,
1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number:
(703) 308-3194; e-mail address: brothers.shaja@epa.gov.
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 codes 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-924. 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, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal
[[Page 16603]]
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-924 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, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., 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, Crystal Mall #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.
3. Electronically. You may submit your comments electronically by
e-mail to: ``opp-docket@epa.gov,'' 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-924. 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 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.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: March 15, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
The 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. Interregional research Project Number 4 (IR-4)
0E6097 and 7F4873
EPA has received pesticide petitions (0E6097 and 7F4873) from IR-4,
Rutgers, The State University of New Jersey, 681 U.S. Highway No. 1
South, North New Brunswick, NJ 08902, and Valent USA Corporation,
Walnut Creek, CA 94596-8025 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 tolerances for residues of
clethodim in or on the following raw agricultural commodities (RAC):
Root vegetables subgroup at 1.0 parts per million (ppm), leaves of root
and tuber vegetables group at 2.0 ppm, leafy petiole vegetables
subgroup at 0.5 ppm, melon subgroup at 2.0 ppm, squash/cucumber
subgroup at 0.5 ppm, cranberry at 0.5 ppm, clover forage at 10 ppm,
clover hay at 20.0 ppm, strawberry at 5.0 ppm, and fruiting vegetables
group at 1.0 ppm.
EPA has determined that the petitions contain 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 support granting of the
petitions. Additional data may be needed before EPA rules on the
petitions. This notice includes a summary of the petitions prepared by
Valent USA Corporation, the registrant, Walnut Creek, CA 94596-8025.
A. Residue Chemistry
1. Plant metabolism. The metabolism of 14C-clethodim
labelled in the ring structure and in the side chain has been studied
in carrots, soybeans, and cotton as well as in lactating goats and
laying hens. The major metabolic pathway in plants is initial
sulfoxidation, forming clethodim sulfoxide, followed by further
oxidation to form clethodim sulfone. These reactions are apparently
followed by elimination of the chloroallyloxy side chain to give the
imine sulfoxide and sulfone, with further hydroxylation to form the 5-
OH sulfoxide and 5-OH sulfone. Clethodim sulfoxide and
[[Page 16604]]
clethodim sulfone conjugates were also detected as major or minor
metabolites, depending on plant species and subfractions. Once the side
chain is cleaved from clethodim, the chloroallyloxy moiety undergoes
extensive metabolism to eliminate chlorine and incorporate three-carbon
moieties into natural plant components.
2. Analytical method. Practical analytical methods for detecting
and measuring levels of clethodim and its metabolites have been
developed and validated in/on all appropriate agricultural commodities,
respective processing fractions, milk, animal tissues, and
environmental samples. The methods have been validated at independent
laboratories, and EPA has successfully performed an analytical method
trial. For most commodities, the primary enforcement method is EPA-RM-
26D-3, an high performance liquid chromotography method capable of
distinguishing clethodim from the structurally related herbicide
sethoxydim.
3. Magnitude of residues. A summary of field residue data
supporting the proposed tolerances on root vegetables subgroup (carrot
and radish), leaves of root and tuber vegetables (sugarbeet tops and
radish tops), leafy petioles (celery), cucurbits (cantaloupe, summer
squash, and cucumber), strawberry, cranberry, and clover is presented
below.
i. Root and tuber vegetables. Eight field trials for carrots were
treated with two post-emergent applications of 0.24 lb. to 0.26 lb.
active ingredient/acre (a.i./acre) and harvested approximately 29 to 31
days after the application. Residues in carrots ranged from 0.25 ppm
to 0.39 ppm total clethodim. Four field trials, radishes were treated
with one post-emergent application of 0.25 lb. a.i./acre and harvested
approximately 14-15 days after application. All residues in radish
roots were less than 0.45 ppm.
ii. Leaves of root and tuber vegetables. Twelve field trials for
sugarbeets were treated with two post-emergent applications of 0.25 lb.
each. Sugar beet tops were harvested approximately 40 days after the
last application. Clethodim residues in/on sugarbeet tops ranged from
0.10 ppm to 0.88 ppm total clethodim.
iii. Leafy petioles. Five field trials for celery was treated with
two post-emergent applications of 0.25 lb. a.i./acre each,
approximately 14 days apart, and harvested approximately 30 days after
the last application. Residues in celery ranged from 0.1 ppm to 0.33
ppm total clethodim.
iv. Cucurbits. Seven field trials for cantaloupes were treated with
two post-emergent applications of 0.25 lb. a.i/acre each and harvested
approximately 13-20 days after the last application. Residues in/on
cantaloupe ranged from 0.10 ppm to 1.2 ppm total clethodim. Six field
trials for summer squash were treated with two post-emergent
applications of 0.25 lb. a.i./acre each and harvested approximately 13-
14 days after the last application. Total clethodim residues ranged
from 0.10 ppm to 0.11 ppm.
v. Strawberry. Seven field trials for strawberries were treated
with two post-emergent applications of 0.23 lb. to 0.27 lb. a.i./acre
each. Strawberry fruit was harvested approximately 4-7 days after the
last application. Clethodim residues in/on sugar beet tops ranged from
0.38 ppm to 2.28 ppm total clethodim.
vi. Cranberry. Three field trials for cranberries were treated with
two post-emergent applications of 0.24 lb. to 0.28 lb. a.i./acre each.
Cranberries were harvested 29-30 days after the last application.
Residues ranged from 0.13 ppm to 3.2 ppm total clethodim.
vii. Clover. Three field trials for clover was treated with one
post-emergent application of 0.25 lb. a.i./acre. Clover forage and hay
were harvested 5 days after the last application. Residues in forage
ranged from 3.3 ppm to 6.1 ppm total clethodim and residues in hay
ranged from 12.2 ppm to 15.3 ppm total clethodim.
viii. Fruiting vegetables. Six field trials for bell peppers were
conducted using two applications of 0.25 lb .a.i./acre and harvested 19
to 21 days after application. Residues in bell peppers ranged from 0.14
ppm to 0.89 ppm total clethodim. Five non-bell pepper field trials were
conducted using two applications of 0.25 lb. a.i./acre and harvested 20
to 22 days after application. Residues in non-bell peppers ranged from
0.12 ppm to 0.92 ppm total clethodim. Combining the data with
previously conducted field trials for tomatoes gives an overall average
residue in fruiting vegetables of 0.42 ppm and supports a tolerance for
fruiting vegetables (except cucurbits) of 1.0 ppm.
B. Toxicological Profile
1. Acute toxicity. Clethodim technical is slightly toxic to animals
following acute oral (Toxicity Category III), dermal (Toxicity Category
IV), or inhalation exposure (Toxicity Category IV). Clethodim is a
moderate eye irritant (Category III), a skin irritant (Category II),
and does not cause skin sensitization in the modified Buehler test in
guinea pigs. In addition, an acute oral no-observed adverse effect
level (NOAEL) has been determined in rats to be 300 milligrams/
kilograms (mg/kg).
2. Genotoxicity. Clethodim does not present a genetic hazard.
Clethodim technical did not induce gene mutation in microbial in vitro
assays. A weak response in an in vitro assay for chromosome aberrations
was not confirmed when clethodim was tested in an in vivo cytogenetics
assay up to the maximally tolerated dose level, nor was the response
observed in vitro using technical material of a higher purity. No
evidence of unscheduled DNA synthesis was seen following in vivo
exposure up to a dose level near the lethal doese LD50 (1.5
g/kg). This evidence indicates that clethodim does not present a
genetic hazard to intact animal systems.
3. Reproductive and developmental toxicity. No reproductive
toxicity was observed with clethodim technical at feeding levels up to
2,500 ppm. Developmental toxicity was observed in two rodent species,
but only at maternally toxic dose levels. Clethodim is therefore, not
considered a reproductive or developmental hazard. These studies
indicate no unique toxicity to the developing fetus or young, growing
animals.
The developmental toxicity study conducted with clethodim technical
in the rat resulted in a developmental and maternal NOAEL and lowest
observed adverse effect level (LOAEL) of 100 and 350 milligrams/
kilograms/day (mg/kg/day), respectively. The NOAEL and LOAEL for
developmental toxicity were based on reductions in fetal body weight
and increases in skeletal anomalies. The developmental toxicity study
conducted with clethodim technical in the rabbit resulted in a maternal
toxicity NOAEL and LOAEL of 25 and 100 mg/kg/day, respectively.
Maternal toxicity was manifested as clinical signs of toxicity and
reduced weight gain and food consumption during treatment.
Developmental toxicity was not observed, and therefore, the
developmental toxicity NOAEL was 300 mg/kg/day, highest dose tested
(HDT). The 2-generation reproduction study conducted with clethodim
technical in the rat resulted in parental toxicity NOAEL and LOAEL of
500 ppm and 2,500 ppm, respectively, based on reductions in body weight
in males, and decreased food consumption in both generations. The NOAEL
for reproductive toxicity was 2,500 ppm, HDT.
4. Subchronic toxicity. Subchronic oral toxicity studies conducted
with clethodim technical in the rat and dog indicate a low level of
toxicity. Effects observed at high dose levels consisted primarily of
decreased body weights,
[[Page 16605]]
increased liver size (increased weight and cell hypertrophy), and
anemia (decreased erythrocyte counts, hemoglobin, or hematocrit) in
rats and dogs. The NOAELs from these studies were 500 ppm milligrams/
kilograms bodyweight/day (ca. 25 mg/kg bwt day) in rats and 25 mg/kg
bwt day in dogs. A 21-day dermal toxicity study in rats with clethodim
technical showed a LOAEL at 100 mg/kg bwt day and a NOAEL at 1,000 mg/
kg bwt day, HDT.
5. Chronic toxicity. Clethodim technical has been tested in chronic
studies with dogs, rats and mice. In chronic studies compound-related
effects noted at high doses included decreased body weight, increased
liver size (liver weight and hypertrophy), and anemia (decreased
hemoglobin, hematocrit, and erythrocyte count). Bone marrow hyperplasia
was observed in dogs at the HDT. No treatment-related increases in
incidence of neoplasms were observed in any study. Chronic NOAELs were
200 ppm for an 18-month feeding study in mice and 500 ppm for a 24-
month study in rats. EPA has established a chronic population adjusted
dose (cPAD) for clethodim of 0.01 mg/kg bwt day, based on the NOAEL in
the 1-year oral dog study and an uncertainty factor of 100. Effects
observed at the LOAEL include, alterations in hematology and increased
absolute and relative liver weights at 75 mg/kg/day.
6. Animal metabolism. Ruminant and poultry metabolism studies
demonstrated that transfer of administered 14C-clethodim
residues to tissues was low. Total 14C-residues in goat
milk, muscle and tissues accounted for less than 0.5% of the
administered dose (24 ppm in diet for 3 days), and were less than 0.4
ppm in all cases. In poultry treated at 2.2 mg/kg/day for 5 days, total
14C-residues in eggs, muscle, and most tissues were less
than 0.3 ppm, although higher in liver, kidney and the GI tract.
Residues in eggs were less than 0.2 ppm.
Comparing metabolites detected and quantified from plant and animal
metabolism studies shows that there are no significant aglycones in
plants which are not also present in the excreta or tissues of animals.
Based on these metabolism studies, the residues of concern in crops and
animal products are clethodim and its metabolites containing the
cyclohexene moiety, and their sulfoxides and sulfones.
7. Metabolite toxicology. Metabolism studies of clethodim in rats,
crop plants, goats and hens demonstrate that the parent is very rapidly
metabolized and, in animals, eliminated. Because parent and metabolites
are not retained in the body, the potential for acute toxicity from in
situ formed metabolites is low. The potential for chronic toxicity is
adequately tested by chronic exposure to the parent at the MTD and
consequent chronic exposure to the internally formed metabolites.
Two metabolites of clethodim, clethodim imine sulfone and clethodim
5-hydroxy sulfone, have been tested in toxicity screening studies to
evaluate the potential impact of these metabolites on the toxicity of
clethodim. In general, these metabolites were found to be less toxic
than clethodim technical for acute and oral toxicity studies;
reproduction and teratology screening studies; and several mutagenicity
studies.
8. Endocrine disruption. No special studies to investigate the
potential for estrogenic or other endocrine effects of clethodim have
been performed. However, a large and detailed toxicology data base
exists for the compound including studies in all required categories.
These studies include acute, sub-chronic, chronic, developmental, and
reproductive toxicology studies including detailed histology and
histopathology of numerous tissues, including endocrine organs,
following repeated or long-term exposure. The results of all of these
studies show no evidence of any endocrine-mediated effects and no
pathology of the endocrine organs. Consequently, Valent USA Corporation
concludes that clethodim does not possess estrogenic or endocrine
disrupting properties.
C. Aggregate Exposure
1. Dietary exposure--i. Food. Chronic dietary exposure to clethodim
residues was calculated for the U.S. population and 26 population
subgroups using anticipated residues (average residues from field
residue studies) and accounting for the percent of the crop treated. A
parallel analysis was performed assuming 100% of the crop treated. In
addition to existing tolerances and those tolerances proposed in this
notice, potential chronic dietary exposure to the following treated
crops and crop groups is also included in this analysis: sunflower,
canola, potato, sweet potato, yam (and other corm and tuberous
vegetables), tomatoes, peppers (all) and other fruiting vegetables.
These additional crops are being proposed for tolerances or
registration by Valent USA Corporation in a separate petition. This
chronic dietary exposure analysis can therefore be used to support both
petitions.
Chronic dietary exposure was at or below 4.5% of the reference dose
(RfD) when accounting for the percent of the crop treated. Calculated
exposure increased to a maximum of 32.1% non-nursing infants ( 1-year
old) using anticipated residues and assuming 100% of the crop treated.
Generally speaking, the Agency has no cause for concern if total
residue contribution for published and proposed tolerances is less than
100% of the cPAD.
ii. Drinking water. Since clethodim is applied outdoors
postemergence to growing agricultural crops, the potential exists for
clethodim and/or its metabolites to reach ground or surface water that
may be used for drinking water. To model very conservative estimates of
the potential concentrations of clethodim and its sulfoxide metabolite
in drinking water, the Agency used SCI-GROW for ground water, and
generic expected environmental concentration (GENEEC) for surface
water. The sum of the parent and metabolite estimated concentrations in
surface water greatly exceeded those in ground water. Dividing the
GENEEC derived 56-day average concentration by three gives 10
micrograms per liter parts per billion (ppb) as the Agency's worse case
estimate for drinking water contamination (April 8, 1998, 63 FR 1701)
(FRL-5784-9). Using standard assumptions about body weight and water
consumption, the chronic exposure from this drinking water would be
0.00029 and 0.001 mg/kg bwt day for adults and children, respectively;
10% of the cPAD for children. Based on this worse case analysis, the
contribution of water to the chronic dietary risk exceeds food, but is
still acceptable.
2. Non-dietary exposure. Clethodim is currently registered for use
on the following residential non-food sites: ornamental plants, wooden
containers for growing plants, along driveways, patios, golf course
turf, walkways, trails, and paths. There are no indoor uses registered
for clethodim. Clethodim kills grassey weeds and does not control
broadleaf weeds. Therefore, clethodim is not used broadcast on turf,
but only on edges and walkways, thus greatly reducing the risk of
residential exposure. There is one exception, under several State 24(c)
registrations clethodim can be used broadcast on winter dormant
perennial turf to control annual grasses. It is conceivable that these
outdoor uses could result in acute or short-term residential exposure.
However, under current EPA criteria, the registered and proposed uses
of clethodim would not constitute a chronic residential exposure
scenario. The Agency did calculate that these potential exposures to
homeowner
[[Page 16606]]
applicators and other potential exposed individuals lead to acceptable
Margin of Exposure (MOE) (63 FR 1701). However, because the Agency did
not identify short- or intermediate-term dermal toxic endpoints of
concern, these risk analyses are no longer necessary.
D. Cumulative Effects
There are other pesticidal compounds that are structurally related
to clethodim including sethoxydim, cycloxydim, and tralkoxydim.
Analytical methods convert some of these herbicides and their
metabolites to common moieties. Plant and animal metabolism data
demonstrates that no common metabolites are formed. In consideration of
potential cumulative effects of clethodim and other substances that may
have a common mechanism of toxicity, there are currently no available
data or other reliable information indicating that any toxic effects
produced by clethodim would be cumulative with those of other chemical
compounds. Thus, only the potential risks of clethodim have been
considered in this assessment of aggregate exposure and effects.
Valent USA Corporation will submit information for EPA to consider
concerning potential cumulative effects of clethodim consistent with
the schedule established by EPA on August 4, 1997 (62 FR 42020) (FRL-
5734-6), and other subsequent EPA publications pursuant to the Food
Quality Protection Act.
E. Safety Determination
1. U.S. population--chronic exposure and risk--i. Adult sub-
populations. Using the dietary exposure assessment procedures described
above for clethodim, calculated chronic dietary exposure -- taking into
account percent of crop treated and using anticipated residues -- from
existing and proposed uses of clethodim is minimal. The estimated
chronic dietary exposure from food for the overall U.S. population and
many non-child/infant subgroups is 0.000151 to 0.000162 mg/kg bwt day,
1.5 to 1.6% of the cPAD. Addition of the small but worse case potential
chronic exposure from drinking water (calculated above) increases
exposure by 0.0003 mg/kg bwt day and the maximum occupancy of the cPAD
from 1.6% to 4.6%. Generally, the Agency has no cause for concern if
total residue contribution is less than 100% of the cPAD. It can be
concluded that there is a reasonable certainty that no harm will result
to the overall U.S. population and many non-child/ infant subgroups
from aggregate, chronic exposure to clethodim residues.
ii. Acute dietary exposure and risk--Adult sub-populations. An
acute dietary endpoint was not identified. Thus, the risk from acute
aggregate dietary exposure to clethodim is considered to be negligible.
iii. Non-dietary exposure and aggregate risk--Adult sub-
populations. Acute, short-term, and intermediate-term dermal and
inhalation risk assessments for residential exposure to clethodim are
not required because no significant toxicological effects were
observed.
2. Infants and children--i. Safety factor for infants and children.
In assessing the potential for additional sensitivity of infants and
children to residues of clethodim, FFDCA section 408 provides that EPA
shall apply an additional margin of safety, up to ten-fold, for added
protection for infants and children in the case of threshold effects
unless EPA determines that a different margin of safety will be safe
for infants and children.
The toxicological data base for evaluating prenatal and postnatal
toxicity for clethodim is complete with respect to current data
requirements. There are no special prenatal or postnatal toxicity
concerns for infants and children, based on the results of the rat and
rabbit developmental toxicity studies or the 3-generation reproductive
toxicity study in rats. Valent USA Corporation concludes that reliable
data support use of the standard 100-fold uncertainty factor and that
an additional uncertainty factor is not needed for clethodim to be
further protective of infants and children.
ii. Chronic exposure and risk--Infant and child sub-populations.
Using the conservative exposure assumptions described above
(anticipated residues and percent of crop treated), the percentage of
the cPAD that will be utilized by dietary (food only) exposure to
residues of clethodim ranges from 0.7% for nursing infants ( 1-year
old), up to 4.5% for children (1-6 years). Adding the worse case
potential incremental exposure to infants and children from clethodim
in drinking water (0.001 mg/kg bwt day) greatly increases the
aggregate, chronic dietary exposure and the occupancy of the cPAD by
10.0% to 14.5% for children (1-6 years). EPA generally has no concern
for exposures below 100% of the cPAD because the cPAD represents the
level at or below which daily aggregate dietary exposure over a
lifetime will not pose appreciable risks to human health. It can be
concluded that there is a reasonable certainty that no harm will result
to infants and children from aggregate, chronic exposure to clethodim
residues.
iii. Acute dietary exposure and risk--Infant and child sub-
populations. An acute dietary endpoint was not identified. Thus, the
risk from acute aggregate dietary exposure to clethodim is considered
to be negligible.
iv. Non-dietary exposure and aggregate risk--Infant and child sub-
populations. Acute, short-term, and intermediate-term dermal and
inhalation risk assessments for residential exposure to clethodim are
not required because no significant toxicological effects were
observed.
F. International Tolerances
Although some have been proposed, there are no Canadian, Mexican,
or Codex tolerances or maximum residue limits established for
clethodim. There are no conflicts between this proposed action and
international residue limits.
2. Interregional Research Project Number 4 New Jersey Agricultural
Station
8E5026 and 9E6049
EPA has received pesticide petitions (8E5026 and 9E6049) from the
Interregional Research Project Number 4 (IR-4), New Jersey Agricultural
Experiment Station, P.O. Box 231, Rutgers University, New Brunswick, NJ
08903. The petitions propose, 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 fludioxonil 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-
pyrrole-3 carbonitrile).
1. PP 8E5026 proposes the establishment of tolerances for
strawberries at 2.0 ppm; dry bulb onion; great-headed garlic; shallot;
and welsh onion at 0.2 ppm; and green onion and leek at 7.0 ppm.
2 PP 9E6049 proposes the establishment of a tolerance for stone
fruit group at 2.0 ppm.
EPA has determined that the petitions contain 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 support granting of the
petitions. Additional data may be needed before EPA rules on the
petitions. This notice includes a summary of petitions prepared by
Novaris Crop Protection, Inc. (Novartis), Greensboro, North Carolina,
27419.
A. Residue Chemistry
1. Plant metabolism. The metabolism of fludioxonil is adequately
understood
[[Page 16607]]
for the purpose of the proposed tolerances.
2. Analytical method. Novartis, has developed and validated
analytical methodology for enforcement purposes. This method (Novartis
Crop Protection Method AG-597B) has passed an Agency petition method
validation for several commodities and is currently the enforcement
method for fludioxonil. This method has also been forwarded to FDA for
inclusion into PAM II. An extensive database of method validation data
using this method on various crop commodities is available; acceptable
method validation and concurrent method recovery data on stone fruits,
strawberry, and onions were submitted. The validated limit of
quantitation (LOQ) for residues of fludioxonil in/on stone fruit is
0.05 ppm and in/on strawberry and bulb vegetables is 0.02 ppm. For
residues in/on representative rotational crop matrices is 0.01 ppm.
3. Magnitude of residues. The magnitude of residues for fludioxonil
is adequately understood for the purpose of the proposed tolerances.
B. Toxicological Profile
1. Acute toxicity. Fludioxonil and end use formulations have very
low toxicity to the mammalian species by the oral, dermal, or
inhalation route. The dose needed to kill 50% of animals was calculated
to be greater than 5,000 mg/kg (oral), 2,000 mg/kg (dermal), and 2.6
milligrams/liter (mg/L) (inhalation) in these studies. The eye and skin
irritations seen in animals upon acute exposure indicate that no more
than transient and slight irritation. No sensitizing potential was
noted with either the technical material or the formulated product.
2. Genotoxicity. Mutagenicity potential of fludioxonil was tested
in several studies. In the Chinese hamster ovary (CHO) cell assay, some
clastogenic and polyploidogenic effects were seen at or near the
precipitating concentration of the test substance. However, results
were negative in the Ames assay, CHO V79 cell assay, hepatocyte DNA
repair assay, rat hepatocyte micronucleus test, mouse bone marrow test,
and Chinese hamster bone marrow test. A dominant lethal test conducted
in the mouse was also negative.
3. Reproductive and developmental toxicity. Fludioxonil is not a
developmental toxicant and does not affect reproduction or fertility.
No fetal toxicity was observed even at the HDT in both the rabbit (300
mg/kg) and the rat (1,000 mg/kg) developmental toxicity studies. In a
2-generation rat reproduction study, a reduction of pup body weight was
seen at the highest feeding level of 3,000 ppm in the presence of
maternal toxicity. The NOAEL was 300 ppm for both maternal and fetal
toxicity in this study.
4. Subchronic toxicity. In a 90-day dietary toxicity study the
kidney and liver have been identified as target organs. In a subchronic
study in rats, the NOAEL was 10 ppm based on liver toxicity. In a
subchronic study in mice, the NOAEL was 100 ppm based on blue urine (a
metabolite); the maximum tolerated dose was 7,000 ppm. In a subchronic
study in dogs, the NOAEL was 200 ppm based on clinical observations;
the maximum tolerated dose was 8,000 ppm.
5. Chronic toxicity. In an 1-year chronic toxicity study in dogs,
the NOAEL was 100 ppm based on body weight effects; the maximum
tolerated dose was 8,000 ppm. Two 18-month dietary carcinogenicity
studies were performed in mice. While a NOAEL of 1,000 ppm was clearly
established in the first study, its highest feeding level (3,000 ppm)
did not meet the criteria for a maximum tolerated dose. In the second
18-month study, the maximum tolerated dose was determined to be 5,000
ppm based on kidney effects. There were no treatment-related increases
in neoplasia at any dose level tested in either study. In a combined
chronic toxicity/carcinogenicity study in rats, the incidence of liver
tumors in top-dose females (3,000 ppm) was marginally higher than the
concurrent controls but within historical control range. The NOAEL for
chronic toxicity was 1,000 ppm in both sexes.
6. Animal metabolism. The metabolism of fludioxonil in rats is
adequately understood.
7. Metabolite toxicology. The residues of concern for tolerance
setting purposes is the parent compound. Consequently, there is no
additional concern for toxicity of metabolites.
8. Endocrine disruption. Fludioxonil does not belong to a class of
chemicals known for having adverse effects on the endocrine system. No
estrogenic effects have been observed in the various short- and long-
term studies conducted with various mammalian species.
C. Aggregate Exposure
1. Dietary exposure--i. Food. For purposes of assessing the
potential dietary exposure under the proposed tolerance, Novartis has
estimated aggregate exposure based on a Tier I assessment from the
proposed tolerance level of 2.0 ppm in or on stone fruit and strawberry
and 8.0 ppm in or on bulb vegetables including in these petitions, a
pending 1.0 ppm grape tolerance, and all the currently established
fludioxonil tolerances. This is deemed a worse case estimate of dietary
exposure since it is assumed that 100% of all crops for which
tolerances are proposed or established are treated except for
strawberry and bulb vegetables where 50% and 28% market share estimates
were utilized. Further, it was assumed that pesticide residues are
present at the tolerance levels.
ii. Drinking water. Exposure of the general population to residues
of fludioxonil from drinking water is considered unlikely since field
dissipation studies demonstrate the movement of fludioxonil into ground
water does not occur. In addition, EPA has not established a maximum
contaminant level for residues of fludioxonil in drinking water.
2. Non-dietary exposure. Non-occupational exposure for fludioxonil
has not been calculated since the current registration for fludioxonil
is limited to commercial crop production. Since the chemical is not
used in or around the home, Novartis considers the potential for non-
occupational exposure to the general population to be non-existent.
D. Cumulative Effects
Consideration of a common mechanism of toxicity is not appropriate
at this time since Novartis is unaware of any reliable information that
indicates that toxic effects produced by fludioxonil would be
cumulative with those of any other chemical compounds. Consequently,
Novartis is considering the potential risks of only fludioxonil in its
aggregate exposure assessment.
E. Safety Determination
1. U.S. population--i. Acute risk. The risk from acute dietary
exposure to fludioxonil is considered to be very low. Using an acute
reference dose (RfD) of 0.1 mg/kg taken from the maternal toxicology
NOAEL from a rabbit teratology study and a 100 fold safety factor and
highly conservative exposure assumptions, 43.4% of the aRfD is utilized
for the general U.S. population.
ii. Chronic risk. Based on the available chronic toxicity data, EPA
has set the RfD for fludioxonil at 0.03 mg/kg/day. This RfD is based on
a 1-year feeding study in dogs with a NOAEL of 3.3 mg/kg/day (100 ppm)
and an uncertainty factor of 100. No additional uncertainty factor was
judged to be necessary as body weight was the most sensitive indicator
of toxicity in that study. Based on the highly conservative exposure
assumptions described above, only 7.5% of the RfD will be utilized by
the U.S. general population. Therefore,
[[Page 16608]]
based on the completeness and reliability of the toxicity data
supporting these petitions, there is a reasonable certainty that no
harm will result from aggregate exposure to residues of fludioxonil as
a result of these requested tolerances.
2. Infants and children. Infants and children are not expected to
show any particular sensitivity to fludioxonil. This can be
demonstrated by referencing several data points, including the
equivalence of the maternal and fetal toxicity NOAEL in the fludioxonil
2-generation rat study.
i. Acute risk. The risk from acute dietary exposure to fludioxonil
is considered to be very low. Under the highly conservative exposure
assumptions of residue levels being at tolerance level and 100% market
share for the majority of crops with proposed and established
fludioxonil registrations, the utilization of the acute RfD of the most
exposed group is 83.4% (children, 1-6 years).
ii. Chronic risk. Using highly conservative aggregate exposures
23.0% and 19.2% of the RfD were obtained for the most sensitive sub-
populations, non-nursing infants ( 1-year old) and children (1-6
years), respectively. Therefore, a reasonable certainty exists that no
harm will result from aggregate exposure to fludioxonil if the proposed
uses are registered.
F. International Tolerances
There are no Codex maximum residue levels established for residues
of fludioxonil in or on strawberrry, dry bulb onion, green onion, and
stone fruit crop fruit.
[FR Doc. 00-7740 Filed 3-28-00; 8:45 am]
BILLING CODE 6560-50-F
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