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Notice of Filing a Pesticide Petition 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 22, 1999 (Volume 64, Number 245)]
[Notices]
[Page 71767-71774]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr22de99-88]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-903; FRL-6396-2]
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
[[Page 71768]]
pesticide chemicals in or on various food commodities.
DATES: Comments, identified by docket control number PF-903, must be
received on or before January 21, 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-903 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, 401 M St., SW.,
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 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-903. 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-903 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-903. 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
[[Page 71769]]
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 Cosmetic 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: December 10, 1999.
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 view
of the petitioner. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summaries announce 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 and BASF Corporation,
Agricultural
9E6002 and 7F4881
EPA has received a pesticide petition (9E6002) from the
Interregional Research Project Number 4 (IR-4), Center for Minor Crop
Pest Management, Technology Center of New Jersey, Rutgers, the State
University of New Jersey, 681 U.S. Highway #1 South, North Brunswick,
NJ 08902-3390. EPA has also received a pesticide petition (7F4881) from
BASF Corporation, Agricultural Products, P.O. Box 13528, Research
Triangle Park, NC 27709. The petitions propose, 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 a tolerances for
residues of pyridaben 2-tert-butyl-5-(4-tert-butylbenzylthio)-4-
chloropyridazin-3(2H)-one in or on the raw agricultural commodities
(RAC) cranberries (9E6002), and pistachio (7F4881) at 0.5 and 0.05 and
parts per million (ppm). Registration for pyridaben on cranberries
would be limited to areas along the eastern coast in the states of MA,
NJ, ME, NY, CT, NH, VT, RI, and DE based on the geographical
representation of the residue data submitted.
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 supports 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,
BASF Corporation, the registrant, P.O. Box 13528, Research Triangle
Park, NC 27709.
A. Residue Chemistry
1. Plant metabolism. The nature of the residue in plants is
adequately understood. The residue of concern is pyridaben per se as
specified in 40 CFR 180.494.
2. Analytical method. The proposed analytical method involves
extraction, partition, clean-up and detection of residues by gas
chromatography/electron capture detector (GC/ECD).
3. Magnitude of residues. Three cranberry residue trials were
conducted in two states. Residues of pyridaben were measured by GC/ECD.
The method of detection had a limit of detection of 0.05 ppm. Residues
ranged from 0.172 to 0.447. Pistachio use rates will be the same as
almond which have already received a tolerance of 0.05 ppm.. Also,
pending at EPA is a nut crop group tolerance petition including 6
residue trials of pecans showing all residues are below 0.05 ppm.
B. Toxicological Profile
1. Acute toxicity--i. Subpopulation females 13+ years old. The no
observed adverse effect level (NOAEL) is 13 milligrams/kilograms (mg/
kg). In a developmental toxicity study, Sprague-Dawley rats (22/group)
from Charles River, U.K., received NC-129 Pyridaben, 98.0% active
ingredient (a.i.) via gavage at dose levels of 0, 2.5, 5.7, 13.0, or
30.0 mg/kg/day from gestation day 6 through 15, inclusive. Natural
mating was used. Maternal toxicity, observed at 13.0 and 30.0 mg/kg/
day, consisted of decreased body weight (bwt)/weight gain and food
consumption during the dosing period. Based on these effects, the
maternal toxicity lowest observed adverse effect level (LOAEL) is 13.0
mg/kg/day and the maternal toxicity NOAEL is 4.7 mg/kg/day (82% of 5.7
mg/kg/day based on concentration analysis). Developmental toxicity
NOAEL is 13.0 mg/kg/day based on observed decreased fetal (bwt) and
increased incomplete ossification in selected bones at 30.0 mg/kg/day
LOAEL. With the 100 uncertainty factor (UF) (10x for interspecies
extrapolation and 10x for intraspecies variability) the chronic
population adjusted dose (cPAD) for females 13+ is 0.13 mg/kg/day.
ii. General population including infants and children. NOAEL = 50
mg/kg. In an acute neurotoxicity study, CD Rats (10/sex/group) were
administered a single oral dose (gavage) of NC-129 in 1% aqueous
carboxymethyl cellulose of 0 (vehicle), 50, 100, and 200 mg/kg (a.i.
equivalents: 44.3, 79.6, and 190.0 mg/kg for males and 44.5, 99.7, and
190.0 mg/kg bwt for females). The animals were observed for mortality
and clinical signs of toxicity for 14 days post-dosing. During the
first 5 days, compound-related decreases in bwt gain were noted in mid-
dose males (17%) and females (36%) and high-dose males (74%); the high-
dose females lost weight (4 g) during the first 4 days of the
observation period. Food consumption was low in all treated groups on
the day of dosing with severe effects seen in the high-dose males (73%
lower than controls). Dose-dependent increases in clinical signs
(piloerection, hypoactivity, tremors, and partially closed eyes) were
seen in mid-dose males and high-dose males and females. These effects
were reversible by observation day 4. Treatment-related findings in the
functional observational battery consisted of lower body temperature
and reduced motor activity among the high-dose males. No treatment-
related gross or microscopic neuropathologic findings were present. The
NOAEL for systemic toxicity is 50 mg/kg for both sexes. The LOAEL of
100 mg/kg/day is based on systemic toxicity including clinical signs
and decreased food consumption and bwt gain. With the 100 UF the aPAD
for the general population is calculated to be 0.5 mg/kg/day.
2. Subchronic toxicity. The NOAEL is 100 mg/kg/day. In a 21-day
dermal toxicity study, repeated doses of pyridaben were applied
topically to approximately 10% of the body surface area of rats at
doses of 0, 30, 100, 300, or 1,000 mg/kg/day for 21 days.
[[Page 71770]]
Increased squamous cell hyperplasia and/or surface accumulation of
desquamated epithelial cells were noted sporadically in the 100, 300,
and 1,000 mg/kg/day dose groups. These findings appear to be due to
abrasions of the skin when the powdered substance was applied onto the
skin, rather than a dose-related effect. No gross dermal irritation
effects were noted. Based on the results of the study, the systemic
dermal toxicity NOAEL is 100 mg/kg/day. The systemic dermal toxicity
LOAEL is determined to be 300 mg/kg/day based on decreased bwt in the
females. The dermal irritation NOAEL is 100 mg/kg/day. Note: In
agreement, a dermal equivalent dose of 94 mg/kg/day is derived if the
maternal oral NOAEL of 4.7 mg/kg/day (based on decreased bwt gain and
food consumption) in the rat oral developmental toxicity study is
adjusted by the proposed 5% dermal absorption rate.
3. Chronic toxicity. EPA has established the cPAD for pyridaben at
0.005 mg/kg/day. This cPAD is based on a 1 year feeding study in dogs
with a NOAEL of 0.5 mg/kg/day and an uncertainty factor of 100 based on
decreased bwt, emesis, and ptyalism.
4. Animal metabolism. The nature of the residue in animals is
adequately understood. The residue of concern is pyridaben and its
metabolites PB-7 (2-tert-butyl-5-[4-(1-carboxy-1-
methylethyl)benzylthio]-4-chloropyridazin-3(2H)-one) and PB-9 (2-tert-
butyl-4-chloro-5-[4-(1,1-dimethyl-2-hydroxyethyl) benzylthio]-
chloropyridazin-3(2H)-one) as specified in 40 CFR 180.494.
C. Aggregate exposure
1. Dietary exposure--i. Food. From the acute dietary risk
assessment, the calculated exposure yields dietary percentage of the
aPAD for females 13+ years old ranging from 29% for females 13+ years
old--not pregnant, non-nursing, to 42% for females 13+ years old--
pregnant, not nursing. The calculated exposure yields dietary
percentage of the aPAD for the remainder of the population ranging from
9% for males 13-19 years old to 77% for nursing infants > 1 year old.
This risk estimate should be viewed as highly conservative; refinement
using anticipated residue values and percent crop-treated data in
conjunction with a Monte Carlo analysis will result in a lower acute
dietary exposure estimate. In conducting the chronic dietary risk
assessment, the registrant has made somewhat conservative assumptions--
that 100% of cranberries will contain pyridaben residues and those
residues will be at the level of the tolerance plus the ratio of
organosoluble residues to pyridaben, and all commodities having
published and pending pyridaben tolerances will contain pyridaben
regulable residues, those residues will be at the anticipated residue
level for the commodity, no percent crop treated data were used, and
plant anticipated residues will be adjusted using the ratio of
organosoluble residues to pyridaben all of which result in an
overestimation of human dietary exposure. Thus, in making a safety
determination for this tolerance, EPA is taking into account this
conservative exposure estimate.
ii. Drinking water. Based on information currently available to
EPA, pyridaben is immobile and thus unlikely to leach to ground water.
There is no established maximum contaminant level for residues of
pyridaben in drinking water. No health advisory levels for pyridaben in
drinking water have been established. EPA uses the Generic expected
environmental concentration (GENEEC) and SCI-GROW screening models to
estimate surface and ground water concentrations for first-tier
exposure assessments. As screening models designed to estimate the
concentrations found in surface and ground water for use in ecological
risk assessment, they provide upper-bound values on the concentrations
that might be found in ecologically sensitive environments because of
the use of a pesticide. The models predict that as much as 2.3 part per
billion (ppb) and 0.0003 ppb of pyridaben may be found in surface and
ground water, respectively. The modeling data were compared to the
results from modeling equations used to calculate the acute and chronic
drinking water levels of concern (DWLOC) for pyridaben in surface and
ground water.
a. Acute exposure and risk. Acute DWLOCs have been calculated by
EPA at the following amounts: U.S. population 14,000 g/L; adult male
20+ years old 15,000 g/L; adult female 13+, pregnant, non-nursing 2,200
g/L infant < 1g/L, nursing 1,100 g/L.
b. Chronic exposure and risk. Chronic DWLOCs have been calculated
by EPA at the following amounts: U.S. population 140 g/L; adult male,
13-19 years old 160 g/L; adult female 13+, nursing 100 g/L; infant > 1,
non-nursing 7 g/L.
2. Non-dietary exposure. Pyridaben is currently not registered for
use on residential non-food sites.
D. Cumulative Effects
The registrant does not have, at this time, available data to
determine whether pyridaben has a common mechanism of toxicity with
other substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
pyridaben does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
the registrant has not assumed that pyridaben has a common mechanism of
toxicity with other substances.
E. Safety Determination
1. U.S. population--i. Acute risk. Using the published and pending
tolerances, the dietary percentage of the aPAD range from 9% for males
13-19 years old to 77% for nursing infants <ls-thn-eq> 1 year old, with
the U.S. population at 18%. This risk estimate should be viewed as
highly conservative; refinement using additional anticipated residue
values and percent crop-treated data in conjunction with Monte Carlo
analysis will result in a lower acute dietary exposure estimate. The
acute dietary exposure does not exceed EPA's level of concern.
Pyridaben is immobile and thus, unlikely to leach to ground water. The
modeling data for pyridaben in drinking water indicate levels less than
EPA's DWLOC for acute exposure. Since a refined acute risk for food
only would not exceed EPA's levels of concern for acute dietary
exposures and the monitoring and modeling levels in water are less than
the acute DWLOC, the registrant does not expect aggregate acute
exposure to pyridaben will pose an unacceptable risk to human health.
ii. Chronic risk. Using the somewhat conservative anticipated
residue contribution (ARC) exposure assumptions described in Unit
III.B. of this preamble, EPA has concluded that aggregate exposure to
pyridaben from food will utilize 20% of the cPAD for the U.S.
population. The major identifiable subgroup with the highest aggregate
exposure is discussed below. 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. The residues of pyridaben in
drinking water do not exceed EPA's DWLOC. Pyridaben does not have any
residential uses. The registrant does not expect the aggregate exposure
to exceed 100% of the cPAD.
iii. Short-term and intermediate-term risk. Short-term and
intermediate-term aggregate exposure takes into account chronic dietary
food and water (considered to be a background exposure level) plus
indoor and outdoor
[[Page 71771]]
residential uses. Since there are no residential uses, a short-term or
intermediate-term aggregate risk assessment is not required.
iv. Aggregate cancer risk for U.S. population. Since pyridaben has
been classified as a Group E carcinogen ``no evidence of
carcinogenicity to humans,'' a cancer risk assessment is not required.
v. Endocrine disrupter effects. EPA is required to develop a
screening program to determine whether certain substances (including
all pesticides and inerts) ``may have an effect in humans that is
similar to an effect produced by a naturally occurring estrogen, or
such other endocrine effect....'' The Agency is currently working with
interested stakeholders, including other government agencies, public
interest groups, industry and research scientists in developing a
screening and testing program and a priority setting scheme to
implement this program. Congress has allowed 3 years old from the
passage of FQPA (August 3, 1999) to implement this program. At that
time, EPA may require further testing of this a.i and end use products
for endocrine disrupter effects.
vi. Determination of safety. Based on these risk assessments, the
registrant concludes that there is a reasonable certainty that no harm
will result from aggregate exposure to pyridaben residues.
2. Infants and children--i. Safety factor for infants and
children--a. In general. In assessing the potential for additional
sensitivity of infants and children to residues of pyridaben, data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat were considered. The developmental
toxicity studies are designed to evaluate adverse effects on the
developing organism resulting from maternal pesticide exposure during
gestation. Reproduction studies provide information relating to
prenatal and postnatal effects from exposure to pyridaben, effects from
exposure to the pesticide on the reproductive capability of mating
animals and data on systemic toxicity. FFDCA section 408 provides that
EPA shall apply an additional tenfold margin of safety for infants and
children in the case of threshold effects to account for prenatal and
postnatal toxicity and the completeness of the data base unless EPA
determines that a different margin of safety will be safe for infants
and children. Margins of safety are incorporated into EPA risk
assessments either directly through use of a margin of exposure (MOE)
analysis or through using uncertainty (safety) factors in calculating a
dose level that poses no appreciable risk to humans. EPA believes that
reliable data support using the standard MOE and UF (usually 100 for
combined interspecies and intraspecies variability) and not the
additional tenfold MOE/UF when EPA has a complete data base under
existing guidelines and when the severity of the effect in infants or
children or the potency or unusual toxic properties of a compound do
not raise concerns regarding the adequacy of the standard MOE/safety
factor.
ii. Developmental toxicity studies--a. Rats. In a developmental
toxicity study in rats, the maternal (systemic) NOAEL was 4.7 mg/kg/
day. The maternal LOAEL of 13 mg/kg/day was based on decreases in bwt,
bwt gain, and food consumption during the dosing period (GD 6-15). The
developmental (fetal) NOAEL was 13 mg/kg/day. The developmental LOAEL
of 30 mg/kg/day was based on decreased fetal bwt and increased
incomplete ossification in selected bones.
b. Rabbits. In an oral developmental toxicity study in rabbits, the
maternal (systemic) NOAEL was not established. The maternal LOAEL of
1.5 mg/kg/day was based on decreases in bwt gain and food consumption.
There was no developmental toxicity observed at any dose tested.
Therefore, the developmental (fetal) NOAEL is 15 mg/kg/day at the
highest dose tested (HDT).
iii. Reproductive toxicity study--rats. In the 2-generation
reproductive toxicity study in rats, the prenatal (systemic) NOAEL was
2.3 mg/kg/day. The prenatal (systemic) LOAEL of 7 mg/kg/day was based
on decreased bwt, decreased bwt gains, and decreased food efficiency.
The reproductive (pup) NOAEL was 7 mg/kg/day and the LOAEL was 7 mg/kg/
day at the HDT.
iv. Prenatal and postnatal sensitivity. The toxicological data base
for evaluating prenatal and postnatal toxicity for pyridaben is
complete with respect to current data requirements. There are no
prenatal or postnatal toxicity concerns for infants and children based
on the results of the rat and rabbit developmental toxicity studies as
well as the 2-generation rat reproductive toxicity study. According to
the above, reliable data support removing the additional 10x safety
factor for protection of infants and children.
v. Conclusion. There is a complete toxicity data base for pyridaben
and exposure data are complete or are estimated based on data that
reasonably accounts for potential exposures.
a. Acute risk. Using the somewhat conservative exposure assumptions
described above, the percentage of the aPAD that will be utilized by
dietary exposure to residues of pyridaben for infants and children
range from 16% for children 7-12 years old to 77% for nursing infants
<ls-thn-eq> 1 year old. The acute DWLOC does not exceed EPA's level of
concern. Taking into account the completeness and reliability of the
toxicity data and this conservative exposure assessment, the registrant
concludes that there is a reasonable certainty that no harm will result
to infants and children from acute aggregate exposure to pyridaben
residues.
b. Chronic risk. Using the somewhat conservative exposure
assumptions described above, EPA has calculated that the percentage of
the cPAD that will be utilized by dietary exposure to residues of
pyridaben ranges from 27% for nursing infants less than 1 year old, up
to 85% for non-nursing infants less than 1 year old. The chronic DWLOC
does not exceed the level of concern. There are no residential uses for
pyridaben. Taking into account the completeness and reliability of the
toxicity data and this conservative exposure assessment, the registrant
concludes that there is a reasonable certainty that no harm will result
to infants and children from chronic aggregate exposure to pyridaben
residues.
c. Short-term or intermediate-term risk. Short-term and
intermediate-term aggregate exposure takes into account chronic dietary
food and water plus indoor and outdoor residential uses. Since the
chronic food and chronic DWLOC do not exceed EPA's level of concern and
there are currently no indoor or outdoor residential uses of pyridaben,
the short-term and intermediate-term aggregate risk does not exceed
EPA's level of concern.
d. Determination of safety. Based on these risk assessments, the
registrant concludes that there is a reasonable certainty that no harm
will result to infants and children from aggregate exposure to
pyridaben residues.
F. International Tolerances
There are no CODEX, Canadian, or Mexican Maximum Residue Limits
established for pyridaben on cranberries and pistachio.
2. Interregional Research Project Number 4
9E6016, 9E6030, 9E6031, and 9E6034
EPA has received pesticide petitions (9E6016, 9E6030, 9E6031, and
9E6034) from the Interregional Project Number 4 (IR-4) Rutgers
University, New Brunswick, NJ, 08903-0231 proposing,
[[Page 71772]]
pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40
CFR part 180 by establishing a tolerance for residues of [bifenthrin,
((2-methyl [1,1'-biphenyl]-3-yl) methyl-3-(2-chloro-3,3,3,-trifluoro-1-
propenyl)-2,2-dimethylcyclopropanecarboxylate) in or on the RAC as
follows:
1. PP 9E6016 proposes the establishment of a tolerance for grape at
0.2 ppm.
2. PP 9E6030 proposes the establishment of a tolerance for peppers
at 0.5 ppm.
3. PP 9E6031 proposes the establishment of a tolerance for head
lettuce at 2.0 ppm.
4. PP 9E6034 proposes the establishment of a tolerance for the
caneberry subgroup 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 supports granting of the
petitions. Additional data may be needed before EPA rules on these
petitions.
A. Residue Chemistry
1. Plant metabolism. The metabolism of bifenthrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabelled bifenthrin in various crops all showing
similar results. The residue of concern is the parent compound only.
2. Analytical method. There is a practical analytical method for
detecting and measuring levels of bifenthrin in or on food with a limit
of detection that allows monitoring of food with residues at or above
the levels set in these tolerances GC/ECD analytical method P-2132M.
3. Magnitude of residues. Field residue trials meeting EPA study
requirements have been conducted at the maximum label rate for these
crops. Results from these trials demonstrate that the proposed
bifenthrin tolerances of 0.2 ppm for grape, 0.5 ppm for peppers, 2.0
ppm for head lettuce, and 1.0 ppm for the caneberry subgroup will not
be exceeded when the product is applied following the proposed use
directions.
B. Toxicological Profile
1. Acute toxicity. For the purposes of assessing acute dietary
risk, FMC has used the maternal NOAEL of 1.0 mg/kg/day from the oral
developmental toxicity study in rats. The maternal LOAEL of this study
of 2.0 mg/kg/day was based on tremors from day 7-17 of dosing. This
acute dietary endpoint is used to determine acute dietary risks to all
population subgroups.
2. Genotoxicity. The following genotoxicity tests were all
negative: gene mutation in Salmonella (Ames); chromosomal aberrations
in Chinese hamster ovary (CHO) and rat bone marrow cells; hypoxanthine
guanine phophoribosyl transferase (HGPRT) locus mutation in mouse
lymphoma cells; and unscheduled DNA synthesis in rat hepatocytes.
3. Reproductive and developmental toxicity. In the rat reproduction
study, parental toxicity occurred as decreased bwt at 5.0 mg/kg/day
with a NOAEL of 3.0 mg/kg/day. There were no developmental (pup) or
reproductive effects up to 5.0 mg/kg/day HDT.
4. Subchronic toxicity. The maternal NOAEL of 1.0 mg/kg/day from
the oral developmental toxicity study in rats is also used for short-
term and intermediate-term MOE calculations (as well as acute,
discussed in paragraph (1) above). The maternal LOAEL of this study of
2.0 mg/kg/day was based on tremors from day 7-17 of dosing.
5. Chronic toxicity--i. The chronic population adjusted dose (cPAD)
has been established at 0.015 mg/kg/day. This cPAD is based on a 1 year
oral feeding study in dogs with a NOAEL of 1.5 mg/kg/day, based on
intermittent tremors observed at the LOAEL of 3.0 mg/kg/day; an
uncertainty factor of 100 is used.
ii. Bifenthrin is classified as a Group C chemical (possible human
carcinogen) based upon urinary bladder tumors in mice; assignment of a
Q* has not been recommended.
6. Animal metabolism. The metabolism of bifenthrin in animals is
adequately understood. Metabolism studies in rats with single doses
demonstrated that about 90% of the parent compound and its hydroxylated
metabolites are excreted.
7. Metabolite toxicology. The Agency has previously determined that
the metabolites of bifenthrin are not of toxicological concern and need
not be included in the tolerance expression.
8. Endocrine disruption. No special studies investigating potential
estrogenic or other endocrine effects of bifenthrin have been
conducted. However, no evidence of such effects were reported in the
standard battery of required toxicology studies which have been
completed and found acceptable. Based on these studies, there is no
evidence to suggest that bifenthrin has an adverse effect on the
endocrine system.
C. Aggregate Exposure
1. Dietary exposure--i. Food. Tolerances have been established for
the residues of bifenthrin, in or on a variety of RACs. Tolerances, in
support of registrations, currently exist for residues of bifenthrin on
hops; strawberries; corn grain, forage, and fodder; cottonseed;
artichokes, the crop group cucurbit vegetables, the crop group legume
vegetables - subgroup edible-podded legume vegetables and subgroup
succulent shelled pea and bean, eggplant, the subgroup head and stem
brassica, and livestock commodities of cattle, goats, hogs, horses,
sheep, poultry, eggs, and milk. Pending tolerances for citrus,
raspberries and sweet corn also exist. For the purposes of assessing
the potential dietary exposure for the existing and pending tolerances,
FMC has utilized available information on anticipated residues,
monitoring data and percent crop treated.
ii. Drinking water. Laboratory and field data have demonstrated
that bifenthrin is immobile in soil and will not leach into ground
water. Other data show that bifenthrin is virtually insoluble in water
and extremely lipophilic. As a result, FMC concludes that residues
reaching surface waters from field runoff will quickly adsorb to
sediment particles and be partitioned from the water column. Further, a
screening evaluation of leaching potential of a typical pyrethroid was
conducted using EPA's Pesticide Root Zone Model (PRZM3). Based on this
screening assessment, the potential concentrations of a pyrethroid in
ground water at depths of 1 and 2 meters are essentially zero [< 0.001
parts per billion (ppb)]. Surface water concentrations for pyrethroids
were estimated using PRZM3 and Exposure Analysis Modeling System
(EXAMS) using standard EPA cotton runoff and Mississippi pond
scenarios. The maximum concentration predicted in the simulated pond
was 0.052 ppb. Concentrations in actual drinking water would be much
lower than the levels predicted in the hypothetical, small, stagnant
farm pond model since drinking water derived from surface water would
normally be treated before consumption. Based on these analyses, the
contribution of water to the dietary risk estimate is negligible.
Therefore, FMC concludes that together these data indicate that
residues are not expected to occur in drinking water.
2. Non-dietary exposure. Analyses were conducted which included an
evaluation of potential non-dietary (residential) applicator, post-
application
[[Page 71773]]
and chronic dietary aggregate exposures associated with bifenthrin
products used for residential flea infestation control and
agricultural/commercial applications. The aggregate analysis
conservatively assumes that a person is concurrently exposed to the
same active ingredient via the use of consumer or professional flea
infestation control products and to chronic level residues in the diet.
In the case of potential non-dietary health risks, conservative point
estimates of non-dietary exposures, expressed as total systemic
absorbed dose (summed across inhalation and incidental ingestion
routes) for each relevant product use category (i.e., lawn care) and
receptor subpopulation (i.e., adults, children 1-6 years old and
infants > 1 year old) are compared to the systemic absorbed dose NOAEL
for bifenthrin to provide estimates of the MOEs. Based on the toxicity
endpoints selected by EPA for bifenthrin, inhalation and incidental
oral ingestion absorbed doses were combined and compared to the
relevant systemic NOAEL for estimating MOEs. In the case of potential
aggregate health risks, the above mentioned conservative point
estimates of inhalation and incidental ingestion non-dietary exposure
(expressed as systemic absorbed dose) are combined with estimates
(arithmetic mean values) of chronic average dietary (oral) absorbed
doses. These aggregate absorbed dose estimates are also provided for
adults, children 1-6 years old and infants > 1 year old. The combined
or aggregated absorbed dose estimates (summed across non-dietary and
chronic dietary) are then compared with the systemic absorbed dose
NOAEL to provide estimates of aggregate MOEs.
The non-dietary and aggregate (non-dietary + chronic dietary) MOEs
for bifenthrin indicate a substantial degree of safety. The total non-
dietary (inhalation + incidental ingestion) MOEs for post-application
exposure for the lawn care product evaluated was estimated to be >
194,000 for adults, 52,400 for children 1-6 years old and 56,700 for
infants < 1 year old. The aggregate MOE (inhalation + incidental oral +
chronic dietary, summed across all product use categories) was
estimated to be 2,158 for adults, 579 for children 1-6 years old and
966 for infants (< 1 year old). It can be concluded that the potential
non-dietary and aggregate exposures for bifenthrin are associated with
substantial margins of safety.
D. Cumulative Effects
In consideration of potential cumulative effects of bifenthrin and
other substances that may have a common mechanism of toxicity, to our
knowledge there are currently no available data or other reliable
information indicating that any toxic effects produced by bifenthrin
would be cumulative with those of other chemical compounds; thus only
the potential risks of bifenthrin have been considered in this
assessment of its aggregate exposure. FMC intends to submit information
for EPA to consider concerning potential cumulative effects of
bifenthrin consistent with the schedule established by EPA pursuant to
the Food Quality Protection Act (FQPA).
E. Safety Determination
1. U.S. population--i. Chronic exposure and risk. Based on a
complete and reliable toxicology data base, the acceptable cPAD is
0.015 mg/kg/day, based on a NOAEL of 1.5 mg/kg/day from the chronic dog
study and an uncertainty factor of 100. Available information on
anticipated residues, monitoring data and percent crop treated was
incorporated into an analysis to estimate the anticipaded residue
contribution (ARC) for 26 population subgroups. The ARC is generally
considered a more realistic estimate than an estimate based on
tolerance level residues. The ARC are estimated to be 0.000444 mg/kg
bwt/day and utilize 3.0% of the cPAD for the overall U. S. population.
The ARC for children 7-12 years old and children 1-6 years old
(subgroups most highly exposed) are estimated to be 0.000650 mg/kg bwt/
day and 0.001203 mg/kg bwt/day and utilizes 4.3% and 8.0% of the cPAD,
respectively. Generally speaking, EPA has no cause for concern if the
total dietary exposure from residues for uses for which there are
published and proposed tolerances is less than 100% of the cPAD.
Therefore, FMC concludes that the chronic dietary risk of bifenthrin,
as estimated by the aggregate risk assessment, does not appear to be of
concern.
ii. Acute exposure and risk. Acute dietary exposure risk
assessments are performed for a food-use pesticide if a toxicological
study has indicated the possibility of an effect of concern occurring
as a result of a 1 day or single exposure. For the purposes of
assessing acute dietary risk for bifenthrin, the maternal NOAEL of 1.0
mg/kg/day from the oral developmental toxicity study in rats was used.
The maternal LOAEL of this study of 2.0 mg/kg/day was based on tremors
from day 7-17 of dosing. This acute dietary endpoint was used to
determine acute dietary risks to all population subgroups. Available
information on anticipated residues, monitoring data and percent crop
treated was incorporated into a Tier 3 analysis, using Monte Carlo
modeling for commodities that may be consumed in a single serving.
These assessments show that the MOEs are greater than the EPA standard
of 100 for all subpopulations. The 99.9<SUP>th</SUP> percentile of
exposure for the overall U. S. population was estimated to be 0.005932
mg/kg/day (MOE of 168). The 99.9<SUP>th</SUP> percentile of exposure
for all infants < 1 year old was estimated to be 0.007331 mg/kg/day
(MOE of 136). The 99.9th percentile of exposure for nursing infants < 1
year old was estimated to be 0.004599 mg/kg/day (MOE of 217). The
99.9<SUP>th</SUP> percentile of exposure for non-nursing infants < 1
year old was estimated to be 0.006974 mg/kg/day (MOE of 143). The
99.9<SUP>th</SUP> percentile of exposure for children 1 to 6 years old
was estimated to be 0.009983 mg/kg/day (MOE of 100). Therefore, FMC
concludes that the acute dietary risk of bifenthrin, as estimated by
the dietary risk assessment, does not appear to be of concern.
2. Infants and children--i. General. In assessing the potential for
additional sensitivity of infants and children to residues of
bifenthrin, FMC considered data from developmental toxicity studies in
the rat and rabbit, and a 2-generation reproductive study in the rat.
The developmental toxicity studies are designed to evaluate adverse
effects on the developing organism resulting from pesticide exposure
during prenatal development to one or both parents. Reproduction
studies provide information relating to effects from exposure to the
pesticide on the reproductive capability of mating animals and data on
systemic toxicity. FFDCA section 408 provides that EPA may apply an
additional margin of safety for infants and children in the case of
threshold effects to account for prenatal and postnatal natal toxicity
and the completeness of the data base.
ii. Developmental toxicity studies. In the rabbit developmental
study, there were no developmental effects observed in the fetuses
exposed to bifenthrin. The maternal NOAEL was 2.67 mg/kg/day based on
head and forelimb twitching at the LOAEL of 4 mg/kg/day. In the rat
developmental study, the maternal NOAEL was 1 mg/kg/day, based on
tremors at the LOAEL of 2 mg/kg/day. The developmental (pup) NOAEL was
also 1 mg/kg/day, based upon increased incidence of hydroureter at the
LOAEL 2 mg/kg/day. There were 5/23 (22%) litters affected (5/141
fetuses since each litter only had one affected fetus) in the 2 mg/kg/
day group, compared with zero
[[Page 71774]]
in the control, 1, and 0.5 mg/kg/day groups. According to recent
historical data for this strain of rat, incidence of distended ureter
averaged 11% with a maximum incidence of 90%.
iii. Reproductive toxicity study. In the rat reproduction study,
parental toxicity occurred as decreased bwt at 5.0 mg/kg/day with a
NOAEL of 3.0 mg/kg/day. There were no developmental (pup) or
reproductive effects up to 5.0 mg/kg/day HDT.
iv. Prenatal and postnatal sensitivity--a. Prenatal. Since there
was not a dose-related finding of hydroureter in the rat developmental
study and in the presence of similar incidences in the recent
historical control data, the marginal finding of hydroureter in rat
fetuses at 2 mg/kg/day (in the presence of maternal toxicity) is not
considered a significant developmental finding. Nor does it provide
sufficient evidence of a special dietary risk (either acute or chronic)
for infants and children which would require an additional safety
factor.
b. Postnatal. Based on the absence of pup toxicity up to dose
levels which produced toxicity in the parental animals, there is no
evidence of special postnatal sensitivity to infants and children in
the rat reproduction study.
c. Conclusion. Based on the above, FMC concludes that reliable data
support use of the standard 100-fold uncertainty factor, and that an
additional uncertainty factor is not needed to protect the safety of
infants and children. As stated above, aggregate exposure assessments
utilized less than 10% of the cPAD for either the entire U. S.
population or any of the 26 population subgroups including infants and
children. Therefore, it may be concluded that there is reasonable
certainty that no harm will result to infants and children from
aggregate exposure to bifenthrin residues.
F. International Tolerances
There are no Codex, Canadian, or Mexican residue limits for
residues of bifenthrin in or on grape, peppers (bell and non-bell),
lettuce, and caneberry.
[FR Doc. 99-33035 Filed 12-21-99; 8:45 am]
BILLING CODE 6560-50-F