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Notice of Filing Pesticide Petitions To Establish a Tolerance for Certain Pesticide Chemicals in or on Food
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: December 3, 1999 (Volume 64, Number 232)]
[Notices]
[Page 67905-67912]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03de99-87]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-900; FRL-6392-6]
Notice of Filing Pesticide Petitions 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-900, must be
received on or before January 3, 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'' section. To
ensure proper receipt by EPA, it is imperative that you identify docket
control number PF-900 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Shaja Brothers, Registration
Support Branch, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460; telephone number: (703) 308-3194; and 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 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 in the ``FOR FURTHER INFORMATION
CONTACT'' section.
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-900. 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
[[Page 67906]]
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-900 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, 401 M St., SW., 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-900. 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 in the ``FOR FURTHER INFORMATION
CONTACT'' section.
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 petitions. Additional data
may be needed before EPA rules on the petitions.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: November 29, 1999.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
The petitioner summaries of pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of
petitions 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.
1. Interregional Research Project Number 4
1E4019, 7E4857, and 9E6009
EPA has received pesticide petitions (1E4019, 7E4857, and 9E6009)
from the Interregional Research Project Number 4 (IR-4) New Jersey
Agricultural Experiment Station, Rutgers University, New Brunswick, New
Jersey 08903 proposing, under 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 the herbicide paraquat (1,1-
dimethyl-4,4'-bypyridinium) derived from the application of the
dichloride salt (calculated as the cation) in or on the raw
agricultural commodities (RAC) globe artichoke, dry peas, and persimmon
at 0.05, 0.3, and 0.05 parts per million (ppm), respectively. 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 Zeneca Ag Products, the
registrant, 1800 Concord Pike, P.O. Box 15458, Wilmingtion, Delaware
19850-5458.
[[Page 67907]]
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residue in
plants is adequately understood based on studies depicting the
metabolism of paraquat in carrots and lettuce following pre-emergence
treatments and in potatoes and soybeans following desiccant treatment.
The residue of concern in plants is the parent chemical, paraquat.
2. Analytical method. An adequate analytical method (spectrometric
method) has been accepted and published in the Pesticide Analytical
Manual (PAM Vol. II) for the enforcement of tolerances in plant
commodities.
3. Magnitude of residues. Magnitude of residue data were collected
from three sites in the major globe artichoke producing region of the
United States. No residues exceed the proposed tolerance of 0.05 ppm,
when globe artichokes are treated with 3.0 to 3.6 lb active ingredient/
acre (ai/acre) of paraquat applied as three applications directed
between the rows at approximately 7-day intervals and the last
application 1-day prior to harvest. Residue data have been obtained
from Washington and Idaho which represent 91% of the dry pea production
in the United States. Mature dry peas were treated once with paraquat
at either 0.5 or 1.0 lb ai/acre of paraquat 7 days prior to harvest.
The highest residue recovered in the dry pea was 0.25 ppm. The other
treated samples all had residues of <ls-thn-eq> 0.2 ppm. IR-4 is
requesting the establishment of a tolerance for persimmon based on the
0.05 ppm tolerance established on guava. Applications of paraquat in
persimmon would be the same as those in the Gramoxone Extra label for
use on guava, utilizing a directed, postemergence application.
B. Toxicological Profile
1. Acute toxicity. Acute toxicity studies conducted with the 45.6%
paraquat dichloride technical concentrate give the following results:
oral lethal dose (LD)<INF>50</INF> in the rat of 344 milligrams/
kilograms (mg/kg) (males) and 283 mg/kg (females) (Category II); dermal
LD<INF>50</INF> in the rat of > 2,000 mg/kg for males and females
(Category III); the primary eye irritation study showed corneal
involvement with clearing within 17 days (Category II); and dermal
irritation of slight erythema and edema at 72 hours (Category IV).
Paraquat is not a dermal sensitizer. Acute inhalation studies conducted
to EPA guideline with aerosolized sprays result in lethal concentration
(LC)<INF>50</INF> of 0.6 to 1.4 <greek-m>g paraquat cation/L (Category
I). However, since paraquat dichloride has no measurable vapor
pressure; and hydraulic spray droplets are too large to be respirable,
inhalation exposure is not a concern in practice.
2. Genotoxicty. Paraquat dichloride was not mutagenic in the Ames
test using Salmonella typhinurium strains TA1535, TA1538, TA98, and
TA100; the chromosomal aberrations in the bone marrow test system; or
in the dominant lethal mutagenicity study with CD-1 mice. Additionally,
paraquat dichloride was negative for unscheduled DNA synthesis (UDS) in
rat hepatocyctes in vitro and in vivo. Paraquat was weakly positive in
the mouse lymphoma cell assay only in the presence of metabolic
activation. Paraquat dichloride was weakly positive in mammalian cells
(lymphocytes) and positive in the sister chromatid exchange (SCE) assay
in Chinese hamster lung fibroblasts. Paraquat is non-mutagenic.
3. Reproductive and developmental toxicity. A 3-generation
reproduction study in rats fed diets containing 0, 25, 75, and 150 ppm
(0, 1.25, 3.75 or 7.5 mg of paraquat cation/kg/day, respectively)
showed no effect on body weight gain, food consumption and utilization,
fertility and length of gestation of the F<INF>0</INF>, F<INF>1</INF>,
and F<INF>2</INF> parents at any dose. The no observed adverse effect
level (NOAEL) and lowest observed adverse effect level (LOAEL) for
systemic toxicity are 25 ppm (1.25 mg/kg/day) and 75 ppm (3.75 mg/kg/
day), respectively, expressed as paraquat cation, based on high
mortality due to lung damage. The NOAEL for reproductive toxicity is
<gr-thn-eq> 150 ppm [7.5 mg/kg/day; highest dose tested (HDT)]
expressed as paraquat cation, as there were no reproductive effects
observed.
Two developmental toxicity studies were conducted in rats given
gavage doses of 0, 1, 5, or 10 mg/kg/day and 0, 1, 3, or 8 mg/kg/day,
respectively, expressed as paraquat cation. In the first study, the
NOAEL for maternal toxicity was 1 mg/kg/day based on clinical signs of
toxicity and decreased body weight gain at 5 mg/kg/day (the LOAEL). The
NOAEL for developmental toxicity was set at 5 mg/kg/day based on
delayed ossification of the forelimb and hindlimb digits. In the second
study, the maternal and developmental NOAEL is 8 mg/kg/day HDT as there
were no effects observed at any dose level. Based on both studies, the
overall NOAEL for maternal and developmental toxicity is at least 3 mg/
kg/day.
Two developmental toxicity studies were conducted in mice given
gavage doses of 0, 1, 5, or 10 mg/kg/day and 0, 7.5, 15, or 25 mg/kg/
day paraquat ion, respectively. In the first study, the NOAEL and LOAEL
for maternal toxicity are 5 mg/kg/day and, 10 mg/kg/day, respectively,
based on reductions in body weight gain and death (range-finding
study). The NOAEL and LOAEL for developmental toxicity are 5 mg/kg/day
and 10 mg/kg/day, respectively based on an increased number of litters
and fetuses with partial ossification of the 4th sternebra at 10 mg/kg/
day HDT. Both the maternal and developmental NOAELs are at 15 mg/kg/day
in the second study. The maternal LOAEL of 25 mg paraquat cation/kg/day
is based on death, decreases in body weight and body weight gain, and
other clinical signs. The developmental LOAEL of 25 mg/kg/day is based
on decreases in mean fetal weights, retarded ossification and other
skeletal effects. According to the registrant, the developmental/
maternal NOAEL should be based on the second study and is 15 mg/kg/day.
Paraquat dichloride is not a developmental toxin.
4. Subchronic toxicity. A 90-day feeding study in dogs fed doses of
0, 7, 20, 60, or 120 ppm with a NOAEL of 20 ppm based on lung effects
such as alveolitis and alveolar collapse seen at the LOAEL of 60 ppm. A
21-day inhalation toxicity study in rats were exposed to respirable
aerosols of paraquat at doses of 0, 0.01, 0.1, 0.5, or 1.0 <greek-m>g/L
with a NOAEL of 0.01 <greek-m>g/L and a LOAEL of 0.10 <greek-m>g/L
based on histopathological changes to the epithelium of the larynx and
nasal discharge.
5. Chronic toxicity. In a 12-month feeding study in dogs fed dose
levels of 0, 15, 30, or 50 ppm, expressed as paraquat cation. These
levels corresponded to 0, 0.45, 0.93, or 1.51 mg of paraquat cation/kg/
day, respectively, in male dogs or 0, 0.48, 1.00, or 1.58 mg of
paraquat cation/kg/day, respectively for female dogs. There was a dose-
related increase in the severity and extent of chronic pneumonitis in
the mid-dose and high-dose male and female dogs. This effect was also
noted in the low-dose male group, but was minimal when compared with
the male controls. The systemic NOAEL is 15 ppm (0.45 mg/kg/day for
males and 0.48 mg/kg/day for females, expressed as parquet cation). The
systemic LOAEL is 30 ppm (0.93 mg/kg/day for males and 1.00 mg/kg/day
for females, expressed as paraquat cation).
In a 2-year chronic feeding/carcinogenicity study, rats were fed
doses of paraquat dichloride at 0, 25, 75, or 150 ppm which correspond
to 0, 1.25, 3.75, or 7.5 mg of paraquat cation/kg/day. Paraquat
enhanced the development of ocular lesions in all of the treated
groups. The predominant lesions detected opthalmoscopically
[[Page 67908]]
were lenticular opacities and cataracts. At test week 103, dose-related
statistically significant (P < 0.001) increases in the incidence of
ocular lesions were observed only in the mid-dose and high-dose male
and female groups. Based on these findings, the NOAEL (approximate) and
the LOAEL for systemic toxicity, for both sexes, are 25 ppm (1.25 mg/
kg/day) and 75 ppm (3.75 mg/kg/day), respectively.
In another 2-year chronic feeding/carcinogenicity study, rats were
dosed at 0, 6, 30, 100, or 300 ppm, expressed as paraquat dichloride
(nominal concentrations), equivalent to 0, 0.25, 1.26, 4.15, or 12.25
mg/kg/day, respectively (males) and 0, 0.30, 1.5, 5.12 or 15.29 mg/kg/
day respectively (females), expressed as paraquat dichloride. The
incidence of ocular changes were low and not caused by paraquat in this
study. The systemic NOAEL is 100 ppm of paraquat dichloride (4.15 and
5.12 mg/kg/day, for males and females, respectively); or 3.0 mg/kg/day
(males) and 3.7 mg/kg/day (females), expressed as paraquat cation. The
systemic LOAEL is 300 ppm of paraquat dichloride (12.25 and 15.29 mg/
kg/day, for males and females, respectively); or 9.0 mg/kg/day (males)
and 11.2 mg/kg/day (females), expressed as paraquat cation.
A chronic feeding/carcinogenicity study in rats fed dose levels of
0, 25, 75, or 150 ppm, expressed as paraquat cation (nominal
concentrations). These doses corresponded to 0, 1.25, 3.75, or 7.5 mg
paraquat cation/kg/day, respectively. There was uncertain evidence of
carcinogenicity (squamous cell carcinomas in the head region; ears,
nasal cavity, oral cavity and skin) in males at 7.5 mg/kg/day HDT with
a systemic NOAEL of 1.25 mg/kg/day. Upon submission of additional data
to EPA, the incidence of pulmonary adenomas and carcinomas was well
within historical ranges and it was determined that paraquat was not
carcinogenic in the lungs and head region of the rat.
In another chronic feeding/carcinogenicity study, rats were fed
dose levels of 0, 6, 30, 100, or 300 ppm, expressed as paraquat
dichloride. There were no carcinogenic findings in this study at the
HDT. In a 2-year chronic feeding/concinogenicity study, SPF Swiss
derived mice were fed paraquat dichloride at dose levels of 0, 12.5,
37.5, or 100/125 ppm, expressed as paraquat cation. These rates
correspond to 0, 1.87, 5.62, and 15 mg/kg/day as cation. Because no
toxic signs appeared after 35 weeks of dosing, the 100 ppm level was
increased to 125 ppm at week 36. There were no carcinogenic effects
observed in this study. The systemic NOAEL for both sexes is 12.5 ppm
(1.87 mg/kg/day) and the systemic LOAEL is 37.5 ppm (5.6 mg/kg/day),
each expressed as paraquat cation based on renal tubular degeneration
in males and weight loss and decreased food intake in females.
Paraquat is classified Category E for carcinogenicity (no evidence
of carcinogenicity in animal studies).
6. Animal metabolism. The qualitative nature of the residue in
animals is adequately understood based on the combined studies
conducted with ruminants (goats and cows), swine, and poultry. The
residue of concern in eggs, milk, and poultry and livestock tissues is
the parent, paraquat.
C. Aggregate Exposure
In examining aggregate exposure, FQPA directs EPA to take into
account available information concerning exposures from the pesticide
residue in food and all other exposures for which there is reliable
information. These other sources of exposure include drinking water,
and non-occupational exposures, e.g., to pesticides used in and around
the home. For estimating acute and chronic risks the Agency considers
aggregate exposures from the diet and from drinking water. Exposures
from uses in and around the home that may be short term, intermediate,
or other durations may also be aggregated as appropriate for specific
chemicals.
1. Dietary exposure. For purposes of assessing the potential
dietary exposure under the proposed tolerance, Zeneca has estimated
aggregate exposure based on the tolerance levels of 0.05 ppm, 0.3 ppm,
and 0.05 ppm in or on globe artichokes, dry peas, and persimmons and
from all other established tolerances. Percent crop treated was also
incorporated into the assessment to derive an upper bound anticipated
residue contribution (ARC). The registrant has concluded that there are
no acute endpoints of concern for paraquat, and an acute aggregate
assessment is not required. The chronic population adjusted dose (cPAD)
for chronic dietary assessments is 0.0045 mg/kg/day, based on a NOAEL
of 0.45 mg/kg/day from a 1-year dog study and the addition of a
standard uncertainty factor of 100.
i. Food--chronic dietary assessment. A chronic dietary exposure
analysis was performed using current and reassessed tolerance level
residues, contributions from the proposed tolerance for use on globe
artichoke, cotton, and persimmons and current percent crop treated
information to estimate the ARC for the general population and 22
subgroups. The tolerance in globe artichoke resulted in a ARC of
0.0000001 mg/kg/day (0.002% of the cPAD) for the general population.
The resulting ARC for the general U.S. population from all established
uses is 0.000367 mg/kg/day (8.2% of the cPAD). For children ages 1-6,
the most highly exposed subgroup, the resulting ARC is 0.001077 mg/kg/
day (23.9% of the cPAD).
ii. Acute dietary assessment. The registrant has determined that
current data on paraquat shows no acute dietary endpoint of concern.
Therefore, an acute dietary risk assessment was not conducted for
paraquat.
iii. Drinking water . The Registration Eligibility Document (RED)
for paraquat has stated the following:
Paraquat is not expected to be a contaminant of ground water.
Paraquat dichloride binds strongly to soil clay particles and it did
not leach from the surface in terrestrial field dissipation studies.
There were, however, detections of paraquat in drinking water wells
from two states cited in the Pesticides in Ground Water Database
(1991). These detections are not considered to be representative of
normal paraquat use. Therefore, paraquat is not expected to be a ground
water contaminant or concern based on normal use patterns. Due to its
persistent nature, paraquat could potentially be found in surface water
systems associated with soil particles carried by erosion; however,
paraquat is immobile in most soils, and at very high application rates
(50-1,000x), there was no desorption of paraquat from soils. Based on
paraquat's normal use patterns and unique environmental fate
characteristics, exposures to paraquat in drinking water are not
expected to be obtained from surface water sources. Therefore, the only
exposures considered in aggregate risk assessment for paraquat is
chronic dietary.
2. Non-dietary exposure. Paraquat dichloride has no residential or
other non-occupational uses that might result in non-occupational, non-
dietary exposure for the general population. Paraquat products are
Restricted Use, for use by Certified Applicators only, which means the
general public cannot buy or use paraquat products.
D. Cumulative Effects
In assessing the potential risk from cummulative effects of
paraquat and other chemical substances, the Agency has considered
structural similarities that exist between paraquat and other
bipyridylium compounds such as diquat dibromide. Examination of the
toxicology data bases of paraquat and diquat dibromide, indicates that
the two compounds have clearly different target
[[Page 67909]]
organs. Based on available data, the registrant does not believe that
the toxic effects produced by paraquat would be cumulative with those
of diquat dibromide.
E. Safety Determination
1. U.S. population. Based on the Paraquat RED, the only exposure
route of concern for paraquat is chronic dietary. Using the
conservation assumptions presented earlier, EPA has established a cPAD
of 0.0045 mg/kg/day. This was based on the NOAEL for the 1-year dog
study of 0.45 mg/kg/day and employed a 100-fold uncertainty factor.
Results of this aggregate exposure assessment, which includes EPA's
reassessment of tolerances for existing crops and the tolerance for use
on globe artichokes, dry peas, and persimmons utilize 8.2% of the cPAD.
Generally, exposures below 100% of the cPAD are of no concern because
it represents the level at or below which daily aggregate dietary
exposure over a lifetime will not pose appreciable risk to human
health. Thus, the registrant has concluded that there is reasonable
certainty that no harm will result from aggregate exposures to paraquat
residues.
2. Infants and children. Zeneca has determined that the established
tolerances for paraquat, with amendments and changes as specified in
this notice, meet the safety standards under the FQPA amendments to
section 408(b)(2)(C) for infants and children. The safety determination
for infants and children considers the factors noted above for the
general population, but also takes into account the possibility of
increased dietary exposure due to specific consumption patterns of
infants and children, as well as the possibility of increased
susceptibility to the toxic effects of paraquat residues in this
population subgroup.
In determining whether or not infants and children are particularly
susceptible to toxic effects from paraquat residues, Zeneca considered
the completeness of the data base for developmental and reproductive
effects, the nature and severity of the effects observed, and other
information.
Based on the current data requirements, paraquat has a complete
data base for developmental and reproductive toxicity. In the
developmental studies, effects were seen (delayed ossification in the
forelimb and hindlimb digits) in the fetuses only at the same or higher
dose levels than effects in the mother. In the reproduction study, no
effects on reproductive performance were seen. Also because the NOAELs
from the developmental and reproduction studies were equal to or
greater than the NOAEL used for establishing the cPAD, the registrant
concluded that it is unlikely that there is additional risk concern for
immature or developing organisms. Finally, there is no epidemiological
information suggesting special sensitivity of infants and children to
paraquat. Therefore, the registrant found that an additional safety
factor for infants and children is not warranted for paraquat.
Zeneca estimates that paraquat residues in the diet of non-nursing
infants (less than 1-year) account for 17.6% of the cPAD and 23.9% of
the cPAD for children aged 1-6 years. Further, residues in drinking
water are not expected. Therefore, Zeneca has determined that there is
reasonable certainty that dietary exposure to paraquat will not cause
harm to infants and children.
F. International Tolerances
There is no approved CODEX maximum residue level (MRL) established
for residues of paraquat on globe artichokes, dry peas, and persimmons.
2. Interregional Research Project Number 4
PP 9E6042
EPA has received a pesticide petition (9E6042) from the
Interregional Research Project Number 4 (IR-4), Center for Minor Crop
Pest Management, at the Technology Centre of New Jersey, 681 U.S.
Highway #1, South, North Brunswick, NJ 08902-3390 proposing, pursuant
to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part
180 by establishing a tolerances for residues of fenpropathrin, alpha-
cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate, in or
on the food commodities cucurbit vegetables (Crop Group 9) commodities
at 0.5 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. This notice includes a summary of the petition prepared by
Valent USA Corporation, the registrant, P.O. Box 8025, Walnut Creek, CA
94596-8025.
A. Residue Chemistry
1. Plant metabolism. The plant metabolism of fenpropathrin has been
studied in five different crops: cotton, apple, tomato, cabbage, and
bean. Fenpropathrin, a cyanohydrin ester, has been labeled with
radiocarbon in three positions -- cyclopropyl ring, aryl rings, and
nitrile. The permutations of plant species and radiocarbon label
position yield a total of 17 separate, reviewed studies. Each of the
studies involved foliar treatment of the plants under either greenhouse
or field conditions and, while the actual treatment conditions and
times to harvest and analyses varied from study to study, the results
of the many studies are consistent. The total toxic residue is best
defined as parent, fenpropathrin.
Fenpropathrin remains associated with the site of application and
only traces are found in seeds (e.g., bean or cotton) or in other parts
of the plant not directly exposed to the application. Much of the
parent residue can be removed from the plant material with a mild
hexane/acetone or hexane rinse, demonstrating that the residue is
located on or near the outside surface of the plant material. The
primary metabolic pathway for fenpropathrin in plants is similar to
that in mammals. There are no qualitatively unique plant metabolites;
the primary aglycones are identical in both plants and animals.
2. Analytical method. Adequate analytical methodology is available
to detect and quantify fenpropathrin (and its metabolites) at residue
levels in numerous matrices. The methods use solvent extraction and
partition and/or column chromatography clean-up steps, followed by
separation and quantitation using capillary column gas-liquid
chromatography with flame ionization detection. The extraction
efficiency has been validated using radiocarbon samples from the plant
and animal metabolism studies. The enforcement methods have been
validated at independent laboratories and by EPA. The limit of
quantitation (LOQ) for fenpropathrin is 0.01 ppm.
3. Magnitude of residues. The field residue data to support the
proposed fenpropathrin tolerance on the cucurbit vegetables crop
grouping includes data on melons (cantaloupe) from 10 sites, cucumbers
from 8 sites and summer squash from 7 sites providing data from 25
sites across the United States. Exaggerated rate and residue decline
studies were included. In the samples that fit the proposed use pattern
the average residue is 0.078 ppm with a maximum value of 0.31 ppm.
Samples with measured residue values below the 0.01 ppm LOQ were
assumed, for the purposes of calculation, to contain residue values of
0.005 ppm (1/2 the LOQ).
[[Page 67910]]
B. Toxicological Profile
1. Acute toxicity. Acute toxicity studies with technical
fenpropathrin: Oral lethal dose (LD)<INF>50</INF> in the rat is 54.0
mg/kg for males and 48.5 mg/kg for females - Toxicity Category I;
dermal LD<INF>50</INF> is 1,600 mg/kg for males and 870 mg/kg for
females - Category II; acute inhalation (impossible to generate
sufficient test article vapor or aerosol to elicit toxicity) - Category
IV; primary eye irritation (no corneal involvement, mild iris and
conjunctival irritation) - Category III; and primary dermal irritation
(no irritation) - Category IV. Fenpropathrin is not a sensitizer.
2. Genotoxicty. An Ames Assay was negative for Salmonella TA98,
TA100, TA1535, TA1537, and TA1538; and E. coli WP2uvrA (trp-) with or
without metabolic activation. Sister Chromosome Exchange in Chinese
hamster ovary (CHO) cells there were no increases in sister chromatid
exchanges seen. Cytogenetics in vitro - negative for chromosome
aberrations in CHO cells exposed in vitro to toxic doses (<gr-thn-eq>
30 <greek-m>g/ml) without activation; and to limit of solubility (1,000
<greek-m>g/ml) with activation. In Vitro Assay in Mammalian Cells -
equivocal results - of no concern. DNA Damage/Repair in Bacillus
subtilis - not mutagenic or showing evidence of DNA damage at
<gr-thn-eq> 5,000 <greek-m>g/paper disk.
3. Reproductive and developmental toxicity. A 3-generation
reproduction study was performed with rats dosed with fenpropathrin at
concentrations of 0, 40, 120, or 360 ppm (0, 3.0, 8.9, or 26.9 mg/kg/
day in males; 0, 3.4, 10.1, or 32.0 mg/kg/day in females,
respectively). The parentals (male/female) systemic NOAEL is 40 ppm
(3.0/3.4 mg/kg/day). The systemic LOAEL is 120 ppm (8.9/10.1 mg/kg/day)
based on body tremors with spasmodic muscle twitches, increased
sensitivity and maternal lethality. The reproductive NOAEL is 120 ppm
(8.9/10.1 mg/kg/day), and the reproductive LOAEL is 360 ppm (26.9/32.0
mg/kg/day) based on decrease mean F<INF>1B</INF> pup weight, increased
F<INF>2B</INF> loss. The pups (male/female) developmental NOAEL is 40
ppm (3.0/3.4 mg/kg/day), and the developmental LOAEL is 120 ppm (8.9/
10.1 mg/kg/day) based on body tremors, increased mortality.
In a developmental toxicity study in rats, pregnant female rats
were dosed by gavage on gestation days 6 through 15 at 0 (corn oil
control) 0.4, 1.5, 2.0, 3.0, 6.0, or 10.0 mg/kg/day. The maternal NOAEL
is 6 mg/kg/day and the LOAEL is 10 mg/kg/day based on death,
moribundity, ataxia, sensitivity to external stimuli, spastic jumping,
tremors, prostration, convulsions, hunched posture, squinted eyes,
chromodacryorrhea, and lacrimation. The developmental NOAEL is > 10 mg/
kg/day.
In a developmental toxicity study in rabbits, pregnant female New
Zealand rabbits were dosed by gavage on gestation days 7 through 19 at
0, 4, 12, or 36 mg/kg/day. Maternal NOAEL is 4 mg/kg/day and the
maternal LOAEL is 12 mg/kg/day based on grooming, anorexia, flicking of
the forepaws. The developmental NOAEL is > 36 mg/kg/day highest dose
tested (HDT).
4. Subchronic toxicity. In a subchronic oral toxicity study, rats
were dosed at concentrations of 0, 3, 30, 100, 300, or 600 ppm in the
diet. The LOAEL is 600 ppm (30 mg/kg/day) based on body weight
reduction (female), body tremors, and increased brain (female) and
kidney (male) weights. The NOAEL is 300 ppm (15 mg/kg/day).
5. Chronic toxicity. In a chronic feeding/carcinogenicity study,
rats were dosed at 0, 50, 150, 450, or 600 ppm in the diet (0, 1.93,
5.71, 17.06, or 22.80 mg/kg/day in males, and 0, 2.43, 7.23, 19.45, or
23.98 mg/kg/day in females). There was no evidence of carcinogenicity
at any dose up to and including 600 ppm. The systemic NOAEL (male) is
450 ppm (17.06 mg/kg/day). The systemic NOAEL (female) is 150 ppm (7.23
mg/kg/day), and the systemic LOAEL (male) is 600 ppm based on increased
mortality, body tremors, increased pituitary, kidney, and adrenal
weights. The systemic LOAEL (female) is 450 ppm (19.45 mg/kg/day) based
on increased mortality and body tremors.
In a chronic feeding/carcinogenicity study, mice were fed diets
containing 0, 40, 150, or 600 ppm (0, 3.9, 13.7, or 56.0 mg/kg/day in
males, and 0, 4.2, 16.2, or 65.2 mg/kg/day in females). Mortality was
highest during the final quarter of the study, but the incidence was
similar in all dosed and control groups. No other indications of
toxicity or carcinogenicity were seen. The systemic NOAEL is > 600 ppm
(HDT; male/female, 56.0/65.2 mg/kg/day).
6. Animal metabolism. In a metabolism study in rats, animals were
dosed with fenpropathrin radiolabelled in either the alcohol or acid
portion of the molecule. Rats received 14 daily oral low-doses of 2.5
mg/kg/day of unlabelled fenpropathrin followed by a 15th dose of either
the alcohol or acid radiolabelled fenpropathrin. Groups of rats
received a single dose of either of the two radiolabelled test articles
at 2.5 mg/kg or 25 mg/kg. The major biotransformations included
oxidation at the methyl group of the acid moiety, hydroxylation at the
4'-position of the alcohol moiety, cleavage of the ester linkage, and
conjugation with sulfuric acid or glucuronic acid. Four metabolites
were found in the urine of rats dosed with alcohol labeled
fenpropathrin. The major metabolites were the sulfate conjugate of 3-
(4'-hydroxyphenoxy)benzoic acid and 3-phenoxybenzoic acid (22-44% and
3-9% of the administered dose, respectively). The major urinary
metabolites of the acid-labeled fenpropathrin were TMPA-glucuronic acid
and TMPA-CH<INF>2</INF>OH (11-26% and 6-10% of the administered dose,
respectively). None of the parent chemical was found in urine. The
major elimination products in the feces included the parent chemical
(13-34% of the administered dose) and four metabolites. The fecal
metabolites (and the percentage of administered dose) included
CH<INF>2</INF>OH-fenpropathrin (9-20%), 4'-OH-fenpropathrin (4-11%),
COOH-fenpropathrin (2-7%), and 4'-OH-CH<INF>2</INF>OH-fenpropathrin (2-
7%). There are no qualitatively unique plant metabolites. The primary
aglycones are identical in both plants and animals; the only difference
is in the nature of the conjugating moieties employed.
7. Metabolite toxicology. The metabolism and potential toxicity of
the small amounts of terminal plant metabolites have been tested on
mammals. Glucoside conjugates of 3-phenoxy-benzyl alcohol and 3-
phenoxybenzoic acid, administered orally to rats, were absorbed as the
corresponding aglycones following cleavage of the glycoside linkage in
the gut. The free or reconjugated aglycones were rapidly and completely
eliminated by normal metabolic pathways. The glucose conjugates of 3-
phenoxybenzyl alcohol and 3-phenoxy-benzoic acid are less toxic to mice
than the corresponding aglycones.
8. Endocrine disruption. No special studies to investigate the
potential for estrogenic or other endocrine effects of fenpropathrin
have been performed. However, as summarized above, a large and detailed
toxicology data base exists for the compound in all required
categories. These studies include evaluations of reproduction and
reproductive toxicity and detailed pathology and histology of endocrine
organs following repeated or long-term exposure. According to the
registrant, these studies are considered capable of revealing endocrine
effects and no such effects were observed.
C. Aggregate Exposure
1. Dietary exposure. The chronic population adjusted dose (cPAD) is
established at 0.025 mg/kg/day. The acute population adjusted dose
(aPAD)
[[Page 67911]]
is established at 6.0 mg/kg/day (systemic). Thus, both chronic and
acute dietary exposure and risk analyses are necessary.
Chronic and acute dietary exposure analyses were performed for
fenpropathrin using anticipated residues and accounting for proportion
of the crop treated. The crops included in the analyses are the
cottonseed, currants, peanuts, strawberries, soybeans and grapes, and
the crop groupings head and stem brassica, fruiting vegetables,
cucurbit vegetables, citrus fruits, and pome fruits; processed products
from these crops; and the resulting secondary residues in meat, milk,
and eggs. Currants and soybeans (and soybean products) were entered
into the analyses using tolerance-level residues and 100% or 1% of the
crop treated, respectively. The fruiting vegetables (Crop Group 9), was
substituted for tomatoes in the dietary exposure and risk analyses. IR-
4 is presently working on this use expansion, and a tolerance petition
adding fruiting vegetables and using these same dietary exposure
analyses will be forthcoming. The various proportion of crop treated
values were derived from published marketing data for crops for which
there are existing fenpropathrin uses, and extrapolated from the uses
of other pyrethroid insecticides for pending crops. Proportion of crop
treated was assumed to be equal for all crops in a crop grouping. A
report of these exposure/risk analyses has been submitted to the Agency
including a detailed description of the methodology and assumptions
used.
i. Food. Chronic dietary exposure was at or below 2.7% of the cPAD
with apples and grapes the commodities contributing the most to chronic
exposure. The anticipated residue contribution (ARC) is estimated to be
0.000204 milligrams/kilograms/bodyweight/day (mg/kg/ bwt/day) and
utilize 0.8% of the cPAD for the overall U.S. population. The ARC for
childern 1-6 years old and childern 7-12 years old (subgroups most
highly exposed) are estimated to be 0.000678 mg/kg bwt/day and 0.000325
mg/kg bwt/day and utilizes 2.7 and 1.3% of the cPAD, respectively. The
ARC for females (13+/Nursing) 0.000248 mg/kg bwt/day and utilizes 1.0%
of the cPAD. The ARC for all infants (< 1-year old) and non-nursing
infants (<1-year old) is 0.000243 mg/kg bwt/day and 0.000284 mg/kg bwt/
day respectivley and utilizes 1.0% of the cPAD. The ARC for nursing
infants (< 1-year old) is 0.000103 and utilizes 0.4% of the cPAD.
Generally speaking, the registrant has no cause for concern if total
residue contribution for published and proposed tolerances is less than
100% of the cPAD.
Acute dietary exposure was calculated at the 99.9th percentile of
exposure and margins of exposure ( MOE) were calculated for the U.S.
population and the subpopulations with the highest risk, as follows:
U.S. population (MOE of 490), females (13+) (MOE 927), all infants (MOE
347), nursing infants (< 1) (MOE 384), non-nursing infants (MOE 328),
childern 1-6 years old (MOE 238), and childern 7-12 years old (MOE
410). In all cases, margins of exposure exceed one-hundred.
ii. Drinking water. Since fenpropathrin is applied outdoors to
growing agricultural crops, the potential exists for fenpropathrin or
its metabolites to reach ground or surface water that may be used for
drinking water. Because of the physical properties of fenpropathrin,
the registrant has determined that it is unlikely that fenpropathrin or
its metabolites can leach to potable ground water.
To further quantify potential exposure from drinking water, surface
water concentrations for fenpropathrin were estimated using genetic
expected environmental concentration (GENEEC) 1.2, and the most intense
field use scenario. The average 56-day concentration predicted in the
simulated pond water was 0.22 parts per billion (ppb). The residence
time of fenpropathrin in surface water has been measured and is short.
In pond studies, fenpropathrin half-life in the water column were less
than 1.5 days, thus this 56-day modeled half-lifes probably
considerably overestimates any real surface water concentration. Using
standard assumptions about body weight (bwt) and water consumption, the
chronic exposure from drinking water would be 6.3 x 10<SUP>-6</SUP> and
2.2 x 10<SUP>-5</SUP> mg/kg bwt/day for adults and children,
respectively; less than 0.09% of the cPAD for children. Based on this
worse case analysis, the contribution of water to the dietary risk is
negligible.
2. Non-dietary exposure. Fenpropathrin, as the product TAME 2.4 EC
Spray, is a restricted use material and registered for professional
non-food use both indoors and outdoors on ornamentals and non-bearing
nursery fruit trees. Fenpropathrin has no animal health, homeowner,
turf, termite, indoor pest control, or industrial uses. Quantitative
information concerning human exposure from this ornamental use is not
available, but exposure to the general public from this use of
fenpropathrin is expected to be minimal. No endpoints of concern were
identified for occupational or residential, dermal or inhalation
exposures of any duration. Thus, no risk assessment is needed.
D. Cumulative Effects
Section 408(b)(2)(D)(v) requires that the Agency must consider
``available information'' concerning the cumulative effects of a
particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.'' Available information in this context
include not only toxicity, chemistry, and exposure data, but also
scientific policies and methodologies for understanding common
mechanisms of toxicity and conducting cumulative risk assessments. For
most pesticides, although the Agency has some information in its files
that may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to resolve
the complex scientific issues concerning common mechanism of toxicity
in a meaningful way.
E. Safety Determination
1. U.S. population--i. Chronic risk--adults. Using the dietary
exposure assessment procedures described above for fenpropathrin,
calculated chronic dietary exposure resulting from residue exposure
from existing and proposed uses of fenpropathrin is minimal. The
estimated chronic dietary exposure from food for the overall U.S.
population is less than 1% of the cPAD. Addition of the small but worse
case potential chronic exposure from drinking water (calculated above,
6.3 x 10-6 mg/kg bwt/day) to the highest chronic exposure value from
food increases the maximum occupancy of the cPAD only slightly from
0.99% to 1.02%. Generally, the Agency has no cause for concern if total
residue contribution is less than 100% of the cPAD.
ii. Acute Risk--adults. The potential acute exposure from food to
the U.S. population and various non-child/infant populations subgroups
(shown above) provide MOE values greatly exceeding 100. Addition of the
worse case, but very small ``background'' dietary exposure from water
is not sufficient to change the MOE values significantly. The
registrant concludes that there is a reasonable certainty that no harm
will result to the overall U.S. population from aggregate, acute
exposure to fenpropathrin residues.
2. Infants and children--safety factor for infants and children. In
assessing the potential for additional sensitivity of
[[Page 67912]]
infants and children to residues of fenpropathrin, 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.
i. Chronic risk--infants and children. Using the dietary exposure
assessment procedures described above, calculated chronic dietary
exposure resulting from residue exposure from existing and proposed
uses of fenpropathrin is minimal. The estimated chronic dietary
exposure from food to infant and child subgroups ranges from 2.7%
[children (1-6 years), 0.000678 mg/kg bwt/day] to 0.4% [nursing infants
(< 1-year), 0.000103 mg/kg bwt/day] of the cPAD. Addition of the small
but worse case potential chronic exposure from drinking water
(calculated above, 2.2 x 10<INF>-5</INF> mg/kg bwt/day) to the highest
chronic exposure value from food increases the maximum occupancy of the
cPAD only slightly from 2.7% to 2.8%. The registrant concludes that
there is a reasonable certainty that no harm will result to infant and
child subgroups of the U.S. population from aggregate, chronic exposure
to fenpropathrin residues.
ii. Acute risk--infants and children. The potential acute exposure
from food to the various child and infant population subgroups all
provide MOE values exceeding 100. Addition of the worse-case, but very
small ``background'' dietary exposure from water (2.2 x 10<SUP>-5</SUP>
mg/kg bwt/day) is not sufficient to change the MOE values
significantly. The registrant concludes that there is a reasonable
certainty that no harm will result to infants and children from
aggregate, acute exposure to fenpropathrin residues.
F. International Tolerances
There are no Codex, Canadian, or Mexican residue limits for
residues of fenpropathrin in or on cucurbit vegetables (Crop Group 9).
[FR Doc. 99-31442 Filed 12-2-99; 8:45 am]
BILLING CODE 6560-50-F