Notice of Filing of Pesticide Petitions to Establish Tolerances
for a Certain Pesticide Chemical in or on Food
[Federal Register: July 5, 2000 (Volume 65, Number 129)]
[Notices]
[Page 41455-41460]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05jy00-78]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-948; FRL-6590-6]
Notice of Filing of Pesticide Petitions to Establish Tolerances
for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of 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-948, must be
received on or before August 4, 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-948 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Shaja R. Brothers,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number: (703) 308-3194; e-mail address:
brothers.shaja@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of
Categories NAICS codes potentially
affected entities
------------------------------------------------------------------------
Industry 111 Crop production.
112 Animal production.
311 Food
manufacturing.
32532 Pesticide
manufacturing.
------------------------------------------------------------------------
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under ``FOR FURTHER INFORMATION
CONTACT.''
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'' and then look up the entry for this document under the
``Federal Register--Environmental Documents.'' You can also go directly
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number PF-948. 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-948 in the subject line on the
first page of your response.
1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
[[Page 41456]]
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-948. Electronic comments may
also be filed online at many Federal Depository Libraries.
D. How Should I Handle CBI That I Want to Submit to the Agency?
Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under ``FOR FURTHER INFORMATION
CONTACT.''
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this
notice.
7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.
II. What Action is the Agency Taking?
EPA has received pesticide petitions as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that 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 support 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: June 26, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
The petitioner summaries of the pesticide petitions are printed
below as required by section 408(d)(3) of the FFDCA. The summaries of
the petitions were prepared by the petitioner and represents the view
of the petitioner. 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.
Interregional Research Project Number 4 (IR-4)
9E6041, 0E6101, 0E6102, 0E6104, 0E6106, and 0E6156
EPA has received pesticide petitions 9E6041, 0E6101, 0E6102,
0E6104, 0E6106, and 0E6156 from the Interregional Research Project No.
4, 681 U.S. Highway #1 South, North Brunswick, NJ 08902-3390 proposing,
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing
tolerances for residues of the insecticide imidacloprid, 1-(6-chloro-3-
pyridinyl)methyl-N-nitro-2-imidazolidinimine in or on the following raw
agricultural commodities:
1. PP 9E6041 proposes the establishment of a tolerance for cilantro
at 3.5 parts per million (ppm).
2. PP 0E6101 proposes the establishment of a tolerance for edible
podded bean at 1.0 ppm.
3. PP 0E6102 proposes the establishment of a tolerance for hops at
4.0 ppm.
4. PP 0E6104 proposes the establishment of a tolerance for
succulent shelled bean at 1.0 ppm.
5. PP 0E6106 proposes the establishment of a tolerance for sweet
corn at 0.05 ppm, sweet corn forage at 0.1 ppm, and sweet corn stover
at 0.2 ppm.
6. PP 0E6156 proposes the establishment of a tolerance for turnip
tops (leaves) at 3.5 ppm.
EPA has determined that the petitions contain data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data support granting of the
petitions. Additional data may be needed before EPA rules on the
petitions. This notice includes a summary of the petitions prepared by
Zeneca Ag Products, Wilmington, DE 19850-5458.
A. Residue Chemistry
1. Plant metabolism. The nature of the imidacloprid residue in
plants and livestock is adequately understood. The residues of concern
are combined residues of imidacloprid and it metabolites containing the
6-chloropyridinyl moiety, all calculated as imidacloprid.
2. Analytical method. The analytical method is a common moiety
method for imidacloprid and its metabolites containing the 6-
chloropyridinyl moiety using a permanganate oxidation, silyl
derivatization, and capillary gas chromatography mass spectrometry (GC/
MS) selective ion monitoring. This method has successfully passed a
petition method validation in EPA labs. There is a confirmatory method
specifically for imidacloprid and several metabolites utilizing GC/MS
and high performance liquid chromatography using ultra-violet detection
(HPLC-UV) which has been validated by EPA as well. Imidacloprid and its
metabolites are stable for at least 24 months in the commodities when
frozen.
3. Magnitude of residues-- i. Turnip tops. IR-4 has received
requests from the California, Oregon, Texas, Mississippi, Oklahoma,
Florida, Ohio, and Tennessee agricultural experiment stations for the
registration of imidacloprid on turnip tops (leaves). No
[[Page 41457]]
data are presented in support of this petition; rather, IR-4 requests
that the registrant's Brassica vegetable data be used to support this
request for turnip tops. Turnips are very closely related to the
Brassica vegetables. This request does not include a tolerance for
turnip roots.
ii. Succulent shelled beans. Seven field trials were conducted in
order to provide information on the magnitude of imidacloprid residues
on lima beans following planting application plus three foliar
applications of imidacloprid. Trials were conducted in Maryland, South
Carolina, Georgia, Ohio, California and Washington. Residue levels
ranged from <0.05 ppm to 0.67 ppm. A tolerance of 1.0 ppm is being
proposed by IR-4.
iii. Edible podded beans. Six field trials were conducted in order
to provide information on the magnitude of imidacloprid residues on
snap beans following the planting application plus 3 foliar
applications of imidacloprid. Trials were conducted in South Carolina,
Florida, Wisconsin, Ohio, New York, and Washington. Residue levels
ranged from <0.05 ppm to 0.89 ppm. A tolerance of 1.0 ppm is being
proposed by IR-4.
iv. Sweet corn. IR-4 received a request from New York for
registration of imidacloprid seed treatment on sweet corn. Imidacloprid
is currently registered for use on field corn. Tolerances for kernel +
cob with husk removed (K + CWHR), sweet corn forage and sweet corn
stover were requested based on field corn data and validation of method
on K + CWHR samples.
v. Cilantro. The nature of imidacloprid residues is adequately
understood and an analytical method is available for enforcement
purposes. IR-4 requests that EPA grant an imidacloprid tolerance for
cilantro based on the similarity of cilantro to other leafy non-
Brassica vegetables (especially fresh parsley) for which imidacloprid
is already registered. Based on the available information, and the
currently registered use patterns for leafy non-Brassica vegetables on
the Admire and Provado labels, the establishment of
a tolerance for cilantro (fresh leaves and stems) would protect the
public health, and would not expose man or the environment to
unreasonable adverse effects.
vi. Hops. Based on available data, the proposed use, foliar
treatment of pirimicarb insecticide at the rate of 1 lb (0.5 lb active)
per acre up to a maximum of 1 lb active ingredient/acre (ai/acre) per
year, minimum 7-day pre-harvest interval, should be supported. Based on
the available information, the establishment of the tolerance proposed
in the petition would protect the public health, and would not expose
man or the environment to unreasonable adverse effects, while providing
growers with a safe and effective insectide.
B. Toxicological Profile
1. Acute toxicity. The acute oral lethal dose (LD)50
values for imidacloprid-technical ranged from 424 milligrams/kilograms
(mg/kg) in the male rat and >450 mg/kg in the female rat. The acute
dermal LD50 was >5,000 mg/kg in the rat. The 4-hour rat
inhalation lethal concentration (LC)50 was >5.33 milligram/
Liter (mg/L). Imidacloprid was not irritating to rabbit skin or eyes.
Imidacloprid did not cause skin sensitization in guinea pigs. In an
acute neurotoxicity study, the lowest observed adverse effect level
(LOAEL) = 42 mg/kg body weight (bwt)/day.
2. Genotoxicity. Mutagenicity studies have demonstrated that
imidacloprid is non-mutagenic both in vivo and in vitro.
3. Reproductive and developmental toxicity. In a developmental
toxicity study with Sprague-Dawley rats, groups of pregnant animals
(25/group) received oral administration of imidacloprid (94.2%) at 0,
10, 30, or 100 mg/kg bwt/day during gestation days 6 through 16.
Maternal toxicity was manifested as decreased body weight gain at all
dose levels and reduced food consumption at 100 mg/kg bwt/day. No
treatment-related effects were seen in any of the reproductive
parameters (i.e., Cesarean section evaluation). At 100 mg/kg bwt/day,
developmental toxicity manifested as wavy ribs (fetus =7/149 in treated
vs. 2/158 in controls and litters, 4/25 vs. 1/25). For maternal
toxicity, the LOAEL was 10 mg/kg bwt/day lowest dose tested (LDT) based
on decreased body weight gain; a no observed adverse effect level
(NOAEL) was not established. For developmental toxicity, the NOAEL was
30 mg/kg bwt/day, and the LOAEL was 100 mg/kg bwt/day based on
increased wavy ribs.
In a developmental toxicity study with Chinchilla rabbits, groups
of 16 pregnant does were given oral doses of imidacloprid (94.2%) at 0,
8, 24, or 72 mg/kg bwt/day during gestation days 6 through 18. For
maternal toxicity, the NOAEL was 24 mg/kg bwt/day and the LOAEL was 72
mg/kg bwt/day based on mortality, decreased body weight gain, increased
resorptions, and increased abortions. For developmental toxicity, the
NOAEL was 24 mg/kg bwt/day and the LOAEL was 72 mg/kg bwt/day based on
decreased fetal body weight, increased resorptions, and increased
skeletal abnormalities.
In a 2-generation reproductive toxicity study, imidacloprid (95.3%)
was administered to Wistar/Han rats at dietary levels of 0, 100, 250,
or 700 ppm (0, 7.3, 18.3, or 52.0 mg/kg bwt/day for males and 0, 8.0,
20.5, or 57.4 mg/kg bwt/day for females). For parental/systemic/
reproductive toxicity, the NOAEL was 250 ppm (18.3 mg/kg bwt/day) and
the LOAEL was 750 ppm (52 mg/kg bwt/day), based on decreases in body
weight in both sexes in both generations. Based on these factors, the
parental/systemic/reproductive NOAEL and LOAEL are 250 and 700 ppm,
respectively, based upon the body weight decrements observed in both
sexes in both generations.
4. Subchronic toxicity. In a dermal toxicity study, groups of 5
male and 5 female New Zealand white rabbits received repeated dermal
applications of imidacloprid (95%) at 1,000 mg/kg bwt/day (limit dose),
6-hours/day, 5-days/week for 3-weeks. No dermal or systemic toxicity
was seen. For systemic and dermal toxicity, the NOAEL was >1,000 mg/kg
bwt/day; a LOAEL was not established.
In an oral toxicity study, groups of Fischer 344 rats (12/sex/dose)
were fed diets containing imidacloprid (98.8%) at 0, 150, 1,000, or
3,000 ppm (0, 9.3, 63.3, or 196 mg/kg bwt/day in males and 0, 10.5,
69.3, or 213 mg/kg bwt/day in females, respectively) for 90-days. No
treatment-related effects were seen at 150 ppm. Treatment-related
effects included decreases in body weight gain during the first 4 weeks
of the study at 1,000 ppm (22% in males and 18% in females) and 3,000
ppm (50% in males and 25% in females) with an associated decrease in
forelimb grip strength especially in males. The NOAEL was 150 ppm (9.3
and 10.5 mg/kg bwt/day in males and females, respectively) and the
LOAEL was 1,000 ppm (63.3 and 69.3 mg/kg bwt/day in males and females,
respectively).
In a rat inhalation study (28-day study in which rats were exposed
6 hours/day, 5 days/week for 4 weeks), the NOAEL for imidacloprid was
5.5 mg/m3.
5. Chronic toxicity. In a chronic toxicity study, groups of Beagle
dogs (4/sex/dose) were fed diets containing imidacloprid (94.9%) at 0,
200, or 1,250/2,500 ppm (0, 6.1, 15, or 41/72 mg/kg bwt/day,
respectively) for 52 weeks. The 1,250 ppm dose was increased to 2,500
ppm from week 17 onwards. The threshold NOAEL was 1,250 ppm (41 mg/kg
bwt/day). The LOAEL was 2,500 ppm (72 mg/kg bwt/day) based on increased
cytochrome-P-450 levels in both sexes and was considered to be a
threshold dose. Due
[[Page 41458]]
to the lack of toxicity at 1,250 ppm, a LOAEL was not established in
this study; following the dose increase to the 2,500 ppm level,
toxicity was observed, thus making 1,250 ppm the threshold NOAEL and
2,500 ppm the threshold LOAEL.
6. Animal metabolism. The metabolism of NTN 33893 (imidacloprid) in
rats was reported in seven studies. Data showed that imidacloprid was
rapidly absorbed and eliminated in the excreta (90% of the dose within
24 hours), demonstrating no biologically significant differences
between sexes, dose levels, or route of administration. Elimination was
mainly renal (70-80% of the dose) and fecal (17-25%). The major part of
the fecal activity originated in the bile. Total body accumulation
after 48 hours consisted of 0.5% of the radioactivity with the liver,
kidney, lung, skin and plasma being the major sites of accumulation.
Therefore, bioaccumulation of imidacloprid is low in rats. Maximum
plasma concentration was reached between 1.1 and 2.5 hours. Two major
routes of biotransformation were proposed for imidacloprid. The first
route included an oxidative cleavage of the parent compound rendering
6-chloronicotinic acid and its glycine conjugate. Dechlorination of
this metabolite formed the 6-hydroxynicotinic acid and its mercapturic
acid derivative. The second route included the hydroxylation followed
by elimination of water of the parent compound rendering NTN 35884. A
comparison between [methylene--14C]-imidacloprid and
[imidazolidine-4,5-14C]-imidacloprid showed that while the
rate of excretion was similar, the renal portion was higher with the
imidazolidine-labeled compound. In addition, accumulation in tissues
was generally higher with the imidazolidine-labeled compound. Also, a
comparison between imidacloprid and one of its metabolites, WAK 3839,
showed that the total elimination was the same for both compounds. The
proposed metabolic pathways for these two compounds were different. WAK
3839 was formed following pretreatment (repeated dosing) of
imidacloprid.
7. Endocrine disruption. The toxicology data base for imidacloprid
is current and complete. Studies in this data base include evaluation
of the potential effects on reproduction and development, and an
evaluation of the pathology of the endocrine organs following short-
term or long-term exposure. These studies revealed no primary endocrine
effects due to imidacloprid.
C. Aggregate Exposure
1. Dietary exposure. Assessments were conducted to evaluate
potential risks due to chronic and acute dietary exposure of the U.S.
population and selected population subgroups to residues of
imidacloprid. These analyses cover all registered crops including
rotational crops; uses pending with the EPA on citrus, leafy petiole
crop group, corn, and sweet corn; active and proposed Section 18 uses
on blueberries, cranberries, table beets, strawberries, turnips; new
proposed IR-4 uses on succulent beans, blueberries, turnips and
cilantro; and an import tolerance petition on bananas.
Novigen Sciences, Inc.'s dietary exposure evaluation model
(DEEMTM), which is licensed to Bayer, was used to estimate
the chronic and acute dietary exposure. Version 6.76 was used for the
chronic analysis and version 6.79 for the acute analysis. This software
uses the food consumption data from the 1994-1996 U.S. Department of
Argiculture (USDA) continuing surveys of food intake by individuals
CSFII 1994-1996.
The endpoint for acute dietary risk assessments is based on
neurotoxicity characterized by decreases in motor or locomotor activity
in female rats at 42 mg/kg bwt/day (LOAEL) from an acute neurotoxicity
study. Based on an uncertainty factor (UF) of 10X for interspecies and
10X for intraspecies the acute reference dose (RfD) = 0.42 mg/kg bwt/
day. EPA has determined that an additional UF for FQPA (reduced to 3X)
applies to all population subgroups for acute risk. Application of the
additional 3X safety factor results in an acute population adjusted
dose (aPAD) 0.14 mg/kg bwt/day or a margin of exposure (MOE) of 300.
For chronic dietary analyses, EPA has established the RfD for
imidacloprid at 0.057 mg/kg/day based on a NOAEL of 5.7 mg/kg bwt/day
from a rat chronic toxicity carcinogenicity study and UFs of 10X for
interspecies and 10X for intraspecies. EPA has determined that an UF
for FQPA (reduced to 3X) applies to all population subgroups for
chronic risk. Application of the additional 3X safety factor results in
a chronic population adjusted dose (cPAD) of 0.019 mg/kg bwt/day.
Results from the acute and chronic dietary exposure analyses
described below demonstrate a reasonable certainty that no harm to the
overall U.S. population or any population subgroup will result from the
use of imidacloprid on currently registered and pending uses.
i. Food. Acute and chronic (tier 3) risk assessments were made
using the results of field trials conducted at maximum label
application rates and the shortest post harvest interval (PHI). For
some of the vegetable crops, these residue data were collected at 1.5X
or greater than the maximum label rate of 0.5 lb ai/acre per season. In
addition, no adjustments were made to account for dissipation of
residues during storage, transportation from the field to the consumer,
washing or peeling. Therefore, the actual dietary exposure will be less
than that presented here.
For the chronic analysis, mean field trial residues were
calculated. For the acute Monte Carlo analysis, the entire distribution
of residue field trial data was used for the ``non-blended'' and
``partially-blended'' foods as determined by EPA. For the foods
considered as ``blended'' by EPA, mean field trial residue data were
used. As allowed in EPA's draft guidance for submission of
probabilistic human health exposure assessments one half limit of
detection/limit of quantitation (LOD/LOQ) values were used for all non-
detected values (values below the sensitivity of the method).
ii. Acute. Bayer's acute Monte Carlo dietary exposure assessment
estimated percent of the aPAD and corresponding margins of exposure
(MOE) for the overall U.S. population (all seasons) and various
subpopulations. In this analysis, the exposure for the total U.S.
population was equal to 6.82% of the aPAD at the 99.9th percentile. The
most highly exposed population subgroup, children (1-6 yrs), had an
exposure equal to 13.44% of the aPAD at the 99.9th percentile.
Therefore, the acute dietary exposure estimates are below EPA's level
of concern for the overall U.S. population as well as the various
subpopulations.
iii. Chronic. Bayer's chronic dietary exposure estimated the
percent of the cPAD for the overall U.S. population (all seasons) and
various subpopulations. In this analysis, the exposure for the total
U.S. population was equal to 1.4% of the cPAD. The most highly exposed
population subgroup, children (1-6 yrs), had an exposure equal to 2.7%
of the cPAD. Therefore, the chronic exposure estimates are below EPA's
level of concern for the overall U.S. population as well as the various
subpopulations.
iv. Drinking water. EPA has determined that imidacloprid is
persistent and could potentially leach into ground water. However,
there is no established maximum concentration level (MCL) or health
advisory levels established for imidacloprid in drinking water. EPA's
``pesticides in ground water data base'' has no entry for imidacloprid.
In addition, Bayer is not
[[Page 41459]]
aware of imidacloprid being detected in any wells, ponds, lakes,
streams, etc. from its use in the U.S. In studies conducted in 1995,
imidacloprid was not detected in 17 wells on potato farms in Quebec,
Canada. Therefore, contributions to the dietary burden from residues of
imidacloprid in water would be inconsequential.
2. Non-dietary exposure-- i. Residential turf. Bayer has conducted
an exposure study to address the potential exposures of adults and
children from contact with imidacloprid treated turf. The population
considered to have the greatest potential exposure from contact with
pesticide treated turf soon after pesticides application are young
children. Margins of safety of 7,587 - 41,546 for 10-year-old children
and 6,859 - 45,249 for 5-year-old children were estimated by comparing
dermal exposure doses to the imidacloprid NOAEL of 1,000 mg/kg/day
established in a 15-day dermal toxicity study in rabbits. The estimated
safe residue levels of imidacloprid on treated turf for 10-year-old
children ranged from 5.6 - 38.2 g/cm2 and for 5-year-old
children from 5.1 - 33.5 g/cm2. This compares with the
average imidacloprid transferable residue level of 0.080 g/
cm2 present immediately after the sprays have dried.
According to Bayer, these data indicate that children can safely
contact imidacloprid-treated turf as soon after application as the
spray has dried.
ii. Termiticide. Imidacloprid is registered as a termiticide. Due
to the nature of the treatment for termites, exposure would be limited
to that from inhalation and was evaluated by EPA's Occupational and
Residential Exposure Branch's (OREB) and Bayer. Data indicate that the
margins of safety for the worst case exposures for adults and infants
occupying a treated building who are exposed continuously (24 hours/
day) are 8.0 x 107 and 2.4 x 108, respectively.
According to Bayer, exposure can be considered negligible.
iii. Tobacco smoke. Studies have been conducted to determine
residues in tobacco and the resulting smoke following treatment.
Residues of imidacloprid in cured tobacco following treatment were a
maximum of 31 ppm (7 ppm in fresh leaves). When this tobacco was burned
in a pyrolysis study, only 2% of the initial residue was recovered in
the resulting smoke (main stream plus side stream). This would result
in an inhalation exposure to imidacloprid from smoking of approximately
0.0005 mg per cigarette. Using the measured subacute rat inhalation
NOAEL of 5.5 mg/m3, it is apparent that exposure to
imidacloprid from smoking (direct and/or indirect exposure) would not
be significant.
iv. Pet treatment. Human exposure from the use of imidacloprid to
treat dogs and cats for fleas has been addressed by EPA's OREB who have
concluded that due to the fact that imidacloprid is not an inhalation
or dermal toxicant and that while dermal absorption data are not
available, imidacloprid is not considered to present a hazard via the
dermal route.
D. Cumulative Effects
No other chemicals having the same mechanism of toxicity are
currently registered, therefore, there is no risk from cumulative
effects from other substances with a common mechanism of toxicity.
E. Safety Determination
1. U.S. population. Based on the exposure assessments described
above and on the completeness and reliability of the toxicity data, it
can be concluded that the exposure estimates from all label and pending
uses of imidacloprid are 6.82% of the aPAD and 1.4% of the cPAD for
dietary exposures. EPA generally has no concerns for exposures below
100% of the PAD. Thus, Bayers concludes that there is a reasonable
certainty that no harm will result from aggregate exposure to
imidacloprid residues.
2. Infants and children. In the Federal Register (63 FR 49837,
September 18, 1998) (FRL-6027-1). EPA has assessed the potential for
additional sensitivity of infants and children to residues of
imidacloprid. EPA has considered data from developmental toxicity
studies in the rat and rabbit and a 2-generation reproduction study in
the rat. These studies are discussed under section A (toxicology
profile) above. The developmental toxicity data demonstrated no
increased sensitivity of rats or rabbits to in utero exposure to
imidacloprid. In addition, the multi-generation reproductive toxicity
study did not identify any increased sensitivity of rats to in utero or
postnatal exposure. Parental NOAELs were lower or equivalent to
developmental or offspring NOAELs. 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 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 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 uncertainty factor (usually 100 for combined interspecies and
intraspecies variability) and not the additional tenfold MOE/
uncertainty factor 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.
Although developmental toxicity studies showed no increased
sensitivity in fetuses as compared to maternal animals following in
utero exposures in rats and rabbits, no increased sensitivity in pups
as compared to adults was seen in the 2-generation reproduction
toxicity study in rats, and the toxicology data base is complete as to
core requirements, the EPA has determined that the additional safety
factor for the protection of infants and children will be retained but
reduced to 3X based on the following weight-of-the-evidence
considerations relating to potential sensitivity and completeness of
the data:
i. There is concern for structure activity relationship.
Imidacloprid, a chloronicotinyl compound, is an analog to nicotine and
studies in the published literature suggests that nicotine, when
administered causes developmental toxicity, including functional
deficits, in animals and/or humans that are exposed in utero.
ii. There is evidence that imidacloprid administration causes
neurotoxicity following a single oral dose in the acute study and
alterations in brain weight in rats in the 2-year carcinogenicity
study.
iii. The concern for structure activity relationship along with the
evidence of neurotoxicity dictates the need of a developmental
neurotoxicity study for assessment of potential alterations on
functional development.
Because a developmental neurotoxicity study potentially relates to
both acute and chronic effects in both the mother and the fetus, EPA
has applied the additional UF for FQPA for all population subgroups,
and in both acute and chronic risk assessments.
Based on the exposure assessments described above and on the
[[Page 41460]]
completeness and reliability of the toxicity data, it can be concluded
that the dietary exposure estimates from all label and pending uses of
imidacloprid are 13.44% of the aPAD at the 99.9th percentile and 2.7%
of the cPAD for the most highly exposed population subgroup, children
(1-6 yrs). Thus, Bayer concludes that there is a reasonable certainty
that no harm will result from aggregate exposure to imidacloprid
residues.
F. International Tolerances
No CODEX maximum residue levels have been established for residues
of imidacloprid on any crops at this time.
[FR Doc. 00-16765 Filed 7-3-00; 8:45 am]
BILLING CODE 6560-50-F
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