Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food

Note: EPA no longer updates this information, but it may be useful as a reference or resource.

[Federal Register: July 6, 2001 (Volume 66, Number 130)]
[Notices]
[Page 35619-35623]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06jy01-61]

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ENVIRONMENTAL PROTECTION AGENCY
[PF-1027; FRL-6784-9]

Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food

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 docket control number PF-1027, must be
received on or before August 6, 2001.

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-1027 in the subject line on the first page of your
response.

FOR FURTHER INFORMATION CONTACT: By mail: Shaja R. Brothers,
Registration Division (7505W), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,

[[Page 35620]]

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,'' ``Regulations and Proposed Rules,'' 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-1027. 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 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-1027 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, 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-1027. 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 a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a 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 support granting of the petition. Additional data
may be needed before EPA rules on the petition.

[[Page 35621]]

List of Subjects

Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

Dated: June 20, 2001.
Peter Caulkins,
Acting 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 view of the
petitioners. EPA is publishing the petition summary verbatim without
editing it 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.

Interregional Reseach Project Number 4 (IR-4)

1E6224 and 1E6233

EPA has received pesticide petitions 1E6224 from the Interregional
Research Project Number 4 (IR-4), 681 US Highway #1 South, North
Brunswick, NJ 08902-3390 and 1E6233 from the Taipai Economic and
Cultural Representative Office, 4301 Connecticut Ave., NW., Suite 420,
Washington, DC 20008 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 180.503 by establishing tolerances for residues of
the fungicide, cymoxanil, 2-cyano-N-(ethylamino)carbonyl-2-
(methoxyimino)acetamide in or on the following raw agricultural
commodities (RACs): PP 1E6224 proposes to establish a tolerance on hops
at 1.0 part per million (ppm). PP 1E6233 proposes to establish a
tolerance on imported lychee at 1.0 ppm. This notice includes a summary
of the petitions prepared by DuPont Agricultural Products, PO Box
80038, Wilmington, DE 19880-003. 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.

A. Residue Chemistry

1. Plant metabolism. The plant metabolism of cymoxanil is
adequately understood in the crops of potatoes, tomatoes, and lettuce.
2. Analytical method. An analytical enforcement method is available
for determining cymoxanil in plant residues using HPLC with UV
detection.
3. Magnitude of residues. The magnitude of residues are adequately
understood for lychee and hops.

B. Toxicological Profile

1. Acute toxicity. A battery of acute toxicity tests on technical
cymoxanil and its Toxicity Categories are as follows:

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Study Type Species Results Toxicity Category
----------------------------------------------------------------------------------------------------------------
Oral LD50 Rat 960 mg/kg Category III
----------------------------------------------------------------------------------------------------------------
Dermal LD50 Rabbit £2000 mg/kg Category III
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Inhalation LC50 Rat 5.06 mg/L Category IV
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Eye irritation Rabbit Slight Irritant Category IV
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Dermal irritation Rabbit Not an Irritant Category IV
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Dermal sensitization Guinea pig Not a sensitizer
----------------------------------------------------------------------------------------------------------------

An acute neurotoxicity study was not required with cymoxanil; no
short term or subchronic studies have been observed.
2. Genotoxicity. Cymoxanil was tested in a battery of assays to
evaluate genotoxicity and chromosome aberrations; the results are as
follows:

------------------------------------------------------------------------
Study Test Organisms Results
------------------------------------------------------------------------
Bacterial gene mutation Salmonella Negative
typhimurium
------------------------------------------------------------------------
Mammalian gene mutation in vitro CHO/HGPRT Negative
------------------------------------------------------------------------
Mammalian chromosome CHO Positive
aberrationsin vitro
------------------------------------------------------------------------
Mammalian chromosome aberrations Mouse micronucleus Negative
in vivo
------------------------------------------------------------------------
Unscheduled DNA synthesis in Primary rat Negative
vitro hepatocytes
------------------------------------------------------------------------
Unscheduled DNA synthesis in Primary rat Negative
vivo and Spermatocytes hepatocytes
------------------------------------------------------------------------

Based on the weight-of-evidence, cymoxanil is not considered to be
genotoxic or clastogenic.
3. Reproductive and developmental toxicity. The results of a series
of studies showed no indication of reproductive or developmental
hazards associated with cymoxanil.
In a 2-generation cymoxanil rat reproduction study, the NOAEL for
both parents and offspring was approximately 7 milligrams/kilogram/day,
based on decreased body weight, weight gain and food consumption in
adults and decreased pup weight in offspring at 32 mg/kg/day. There
were no reproductive or fertility effects. Since offspring effects
occurred only in the presence of maternal toxicity, it is considered a
secondary effect to the health effects on the dam.
The developmental studies conducted in rats demonstrated a NOAEL of
10 mg/kg/day, and a LOAEL of 25 mg/kg/day for both adult and
developmental effects. Maternal effects in rats included decreased
weight, weight gain, and food consumption. Developmental effects were
increases in fetal variations, which were the result of generalized
delays in ossification, and overall malformations, although
malformations detected were not dose related.

[[Page 35622]]

In rabbits, several developmental toxicity studies were conducted.
Based on the weight-of-evidence of all three studies, there was no
unique sensitivity of perinatal animals to the effects of cymoxanil,
nor any anomalies of the fetal nervous system at maternally toxic doses
up to and including 32 mg/kg/day.
4. Subchronic toxicity. Subchronic (90-day) feeding studies were
conducted with rats, mice, and dogs. In addition, the following
subchronic feeding studies were conducted: a 90-day in rats to evaluate
neurotoxicity and 28-day rats and mice to evaluate immunotoxicity. A
28-day dermal study was also conducted in rats.
In a subchronic toxicity/neurotoxicity study in rats with
cymoxanil, the NOAEL of 47.6 mg/kg/day in males was based on decreased
body weights, and minimal to mild testicular and epididymal effects at
higher concentrations. In females, the NOAEL of 59.9 mg/kg/day was
based on effects on body weight, weight gain, and food efficiency at
higher levels.
The subchronic NOAEL for male mice administered cymoxanil was 8.25
mg/kg/day based on body weight and weight gain effects at 82.4 mg/kg/
day and above. The NOAEL for females was 121 mg/kg/day based on
increases in spleen and liver weights at 433 mg/kg/day and above.
For cymoxanil, dogs were the most sensitive species in subchronic
studies. Reduced body weight gain and/or food consumption was observed
at 3 mg/kg/day or greater in females and 5 mg/kg/day and above in
males. Both sexes had RBC changes (decreased RBC counts, Hb, and/or
Hct), increased incidence of ketonuria at the intermediate and high
concentration, and changes in serum chemistry (decreases in various
electrolytes and proteins) at the high dose. Males had testicular and
epididymal effects at the highest concentration, 11 mg/kg/day (raised
from 5 mg/kg/day at week 3); this was considered to be retardation of
development due to markedly reduced body weight in this group. The
NOAEL for males was 3 mg/kg/day. There was no NOAEL in female dogs in
the 90-day study. Although a NOAEL was not established in the dog
subchronic study, 3 mg/kg/day was found to be a NOAEL in a subsequent
chronic study in dogs.
Subchronic (28-day) studies were conducted in rats and mice to
evaluate the immunotoxicity potential of cymoxanil. Cymoxanil was not
immunotoxic up to and including the highest dose tested (HDT) which was
1,600 ppm in rats (108 and 117 mg/kg/day in males and females,
respectively), 1,200 ppm (218 mg/kg/day) in male mice, and 2,400 ppm
(552 mg/kg/day) in female mice.
Cymoxanil was applied to the skin of rats 6-hours/day for 28 days
at doses of 0, 50, 500, and 1,000 mg/kg/day. There were no effects at
any dose tested. The 28-day dermal NOAEL was 1,000 mg/kg/day, the HDT.
5. Chronic toxicity. Chronic studies with cymoxanil were conducted
on rats, mice, and dogs to determine carcinogenic potential and/or
chronic toxicity of the compound. Effects generally similar to those
observed in the 90-day studies were seen in the chronic studies;
cymoxanil was not found to be carcinogenic.
The chronic NOAEL for cymoxanil in male rats was 4.08 mg/kg/day
based on decreased body weight, weight gain, food efficiency, and non-
neoplastic lesions in several organs including lung inflammation,
spermatid degeneration, and retinal atrophy at 30.3 mg/kg/day or
higher. In addition, male rats in the two highest groups displayed
increased aggressiveness and hyperreactivity consistent with the
compromised general health status (i.e. systemic toxicity) of those
groups. In females, the NOAEL of 5.36 mg/kg/day was based on decreased
body weight, weight gain, food efficiency, and non-neoplastic lesions
in several organs including lungs, liver, intestines, mesenteric lymph
nodes, sciatic nerve, and retina at 38.4 mg/kg/day or higher. Retinal
atrophy and sciatic lesions are common spontaneous lesions associated
with aging. These effects observed in cymoxanil test animals were
considered aging-related effects. Spermatid degeneration occurs
spontaneously in rats. While the incidence was increased in cymoxanil-
treated rats, most were mild or minimal, and none were more than
moderate. Thus, the effects are considered a mild exacerbation of a
spontaneously occurring lesion.
In mice, the chronic NOAELs for cymoxanil were 4.19 and 5.83 mg/kg/
day for males and females, respectively, based on changes in organ
weights, gastrointestinal effects in females, and liver, testes and
epididymal effects in males at the LOAEL. Similar to the rat, the
testicular effects were considered an exacerbation of a spontaneous
lesion that occurred in one-quarter of the control mice. The LOAELs
were 42.0 and 58.1 mg/kg/day for males and females, respectively.
The chronic cymoxanil NOAEL for male dogs was 3.0 mg/kg/day based
on a temporary decrease in body weight and food consumption, and lower
RBC count, hemoglobin, and hematocrit at 5.7 mg/kg/day. In female dogs
the only finding was a transient effect on body weight, food
consumption, and food efficiency at the HDT, 3.1 mg/kg/day, only during
the first week of the study.
6. Animal metabolism. When administered by gavage to rats,
cymoxanil was readily absorbed and eliminated. Absorption reached
maximum concentrations in whole blood within 4 hours post-dosing. A
rapid and almost complete elimination was observed in the urine and
feces. The majority of radioactivity was recovered within 96 hours,
mainly in urine but also in feces. Radioactivity in the tissues and
carcass was less than 1%. In the urine and feces, the majority of the
radioactivity was free and/or conjugated glycine. 2-Cyano-2-
methoxyimino-acetic acid was also found in low levels in the urine and
trace levels in the feces. Intact cymoxanil was less than 1% in feces
and not detected urine. The metabolite profile in urine and feces was
similar between sexes, among dose groups, and between dosing regimens.
7. Metabolite toxicology. There are no metabolites of toxicological
significance to mammals.
8. Endocrine disruption. The probability of an endocrine effect due
to agricultural uses of cymoxanil is negligible.

C. Aggregate Exposure

1. Dietary exposure. Cymoxanil is a fungicide currently registered
in the United States for use on potatoes. In addition, tolerances have
been approved for cymoxanil on imported tomatoes and grapes.
i. Food. The acute and chronic analysis conservatively assumed that
30% of cucurbits, fruiting vegetables, head lettuce, potatoes and
imported grapes would be treated with cymoxanil and field trial residue
data was used. As reflected in the 1994-1996 USDA CSFII data, neither
hops nor lychee are consumed as part of the diet. Therefore, any
increased exposure from the use of cymoxanil on hops and lychee would
be negligible and would not significantly alter the acute and chronic
dietary risk estimates provided. The analysis' show that adequate
margins of safety exist for all population subgroups, and no effects
would result from dietary exposure to cymoxanil.
a.Acute dietary exposure assessment. The acute dietary exposure
assessment was estimated using Tier 3. The results of the acute dietary
exposure analysis for cymoxanil are given in table below. The
percentages of the acute population adjusted dose (aPAD) for cymoxanil
were calculated based on an acute NOAEL of 4 mg/kg/day from the rabbit

[[Page 35623]]

developmental study based on maternal clinical signs and weight effects
at the higher levels and an uncertainty factor of 100. The results of
the acute dietary exposure analysis are below the EPA's level of
concern.

Results of Acute Dietary Exposure Estimates for Cymoxanil
------------------------------------------------------------------------
99.9th Percentile
Population Group of Exposure (mg/kg/ % aPAD
day)
------------------------------------------------------------------------
U.S. Population 0.001789 4.47
------------------------------------------------------------------------
Non-Nursing ( 1 yr.) 0.000599 1.50
------------------------------------------------------------------------
Children (1-6 yr.) 0.002096 5.24
------------------------------------------------------------------------
Children (7- 12 yr.) 0.001936 4.84
------------------------------------------------------------------------
Females (13+ nursing) 0.002287 5.72
------------------------------------------------------------------------

b. Chronic dietary exposure assessment. The chronic dietary
exposure assessment was estimated using the Dietary Exposure Evaluation
Model (DEEM, Novigen Sciences, Inc., 1999 Version 6.74). The following
table presents the results of an analysis for chronic exposure to
cymoxanil in either TanosR 50DF or CurzateR 60DF. The chronic
population adjusted dose (cPAD) of 0.041 mg/kg/day is based on a NOAEL
of 4.08 mg/kg/day from the one-year rat feeding study and an
uncertainty factor of 100. No sensitive subpopulations were identified.
The results of the chronic dietary exposure analysis are below the
EPA's level of concern.

Results of Chronic Dietary Analysis with Cymoxanil
------------------------------------------------------------------------
Maximum Dietary
Population Group Exposure (mg/kg/ % cPAD
day)
------------------------------------------------------------------------
U.S. Population 0.000063 0.2
------------------------------------------------------------------------
Non-Nursing Infants (1 yr.) 0.000016 0.1
------------------------------------------------------------------------
Children (1-6 yr.) 0.000074 0.2
------------------------------------------------------------------------
Children (7-12 yr.) 0.000068 0.2
------------------------------------------------------------------------
Females (13+) 0.000074 0.2
------------------------------------------------------------------------

ii. Drinking water. Surface water exposure was estimated using the
Generic Expected Environmental Concentration (GENEEC) model. This
screening level model is used for determining upper bound
concentrations of pesticides in surface water.
The acute drinking water level of concern(s) (DWLOCs) are 1.3 ppm
for the U.S. population, and 0.38 ppm for children (1-6 years old), the
most exposed population subgroup. The estimated environmental
concentration (EECs) of cymoxanil in surface water is 8.15 parts per
billion (ppb) derived from GENEEC does not exceed the acute DWLOC.
The chronic DWLOCs are 1.4 ppm for the U.S. population and 0.4 ppm
for children (1-6 years old), the most sensitive subgroup. The GENEEC
56-day EECs of 0.37 ppb does not exceed the chronic DWLOC for cymoxanil
in surface water.
Therefore, based on the above findings, the registrants conclude
with reasonable certainty that residues of cymoxanil in drinking water
do not contribute significantly to the aggregate chronic human health
risk.
2. Non-dietary exposure. Cymoxanil products are not labeled for
residential non-food uses, thereby eliminating the potential for
residential exposure.

D. Cumulative Effects

EPA's consideration of a common mechanism of toxicity is not
necessary at this time because there is no indication that toxic
effects of cymoxanil should be cumulative with those of any other
chemical compounds or with each other.

E. Safety Determination

1. U.S. population. For acute dietary exposure of cymoxanil, the
estimated exposure is 0.000475 and 0.001789 at the 99th and 99.9th
percentiles, which will utilize 1.19 and 4.47%, respectively, of the
acute population adjusted dose (aPAD) for the overall U.S. population.
The chronic dietary exposure for the overall U.S. population is
estimated to be 0.000063 mg/kg/day, using 0.2% of the chronic
population adjusted dose (cPAD). Based on the completeness and
reliability of the toxicity data and the conservative exposure
assessments, there is reasonable certainty that no harm will result
from the aggregate exposure of residues of cymoxanil including all
anticipated dietary exposure and all other non-occupational exposures.
2. Infants and children. For acute dietary exposure of cymoxanil,
the aPAD for children 1-6 years old is 1.44 at the 99th percentile and
5.24 at the 99.9th percentile. For non-nursing infants (1 yr.), the %
aPAD is 0.46 at the 99th percentile and 1.50 at the 99.9th percentile.
Chronic dietary exposure of cymoxanil for the most highly exposed
children's subpopulations are: 0.000074 mg/kg/day for children 1-6
years old, and 0.000068 mg/kg/day for children 7-12 years old,
representing 0.2% of the cPAD for each subpopulation. Exposure for all
infant subpopulations was negligible.
In addition, there are no residential uses of cymoxanil; therefore,
it is extremely unlikely that drinking water will be contaminated.
Based on the completeness and reliability of the toxicity database,
the lack of toxicological endpoints of special concern, the lack of any
indication that children are more sensitive than adults to cymoxanil,
and the conservative exposure assessment, the registrants believe there
is a reasonable certainty that no harm will result to infants and
children from the aggregate exposure of residues of cymoxanil,
including all anticipated dietary exposure and all other non-
occupational exposures. Accordingly, there is no need to apply an
additional safety factor for infants and children.

F. International Tolerances

No international tolerances currently exist for cymoxanil.
[FR Doc.01-16957 Filed 7-5-01; 8:45 am]
BILLING CODE 6560-50-S

Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food

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