[Federal Register Volume 63, Number 181 (Friday, September 18, 1998)]
[Rules and Regulations]
[Pages 49837-49852]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-25085]
=======================================================================
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300717; FRL-6027-1]
RIN 2070-AB78
Imidacloprid; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for the combined
residues of imidacloprid and its metabolites containing the 6-
chloropyridinyl moiety in or on sugar beets (tops, roots, molasses),
barley (grain, straw, hay), wheat (grain, forage, straw, hay), as
requested by Gustafson, Incorporated (PP 5F4584 and PP 4F4337); and
cereal grains crop group (grain, forage, straw, hay, stover), sweet
corn, safflower (seed, meal), legume vegetables crop group (seed,
foliage), soybean meal, as requested by Bayer Corporation (PP 6F4765).
Gustafson, Incorporated, and Bayer Corporation requested these
tolerances under the Federal Food, Drug and Cosmetic Act (FFDCA), as
amended by the Food Quality Protection Act of 1996.
DATES: This regulation is effective September 18, 1998. Objections and
requests for hearings must be received by EPA on or before November 17,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, OPP-300717, must be submitted to: Hearing Clerk
(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,
Washington, DC 20460. Fees accompanying objections and hearing requests
shall be labeled ``Tolerance Petition Fees'' and forwarded to: EPA
Headquarters Accounting Operations Branch, OPP (Tolerance Fees), PO Box
360277M, Pittsburgh, PA 15251. A copy of any objections and hearing
requests filed with the Hearing Clerk identified by the docket control
number, OPP-300717, must also be submitted to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, bring a copy of
objections and hearing requests to Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epamail.epa.gov. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1
or ASCII file format. All copies of objections and hearing requests in
electronic form must be identified by the docket control number OPP-
300717. No Confidential Business Information (CBI) should be submitted
through e-mail. Electronic copies of objections and hearing requests on
this rule may be filed online at many Federal Depository Libraries.
[[Page 49838]]
FOR FURTHER INFORMATION CONTACT: By mail: Peg Perreault, Registration
Division 7505C, Office of Pesticide Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. Office location,
telephone number, and e-mail address: Crystal Mall #2, 1921 Jefferson
Davis Hwy., Arlington, VA, 703-305-5417, e-mail:
Perreault.Peg@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Registers of June 25, 1997
(62 FR 34261) (FRL-5719-6) and February 26, 1997 (62 FR 8731) (FRL-
5589-2), EPA issued notices pursuant to section 408 of the Federal
Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) announcing the
filing of pesticide petitions (PP 5F4584, PP 4F4337, Gustafson; and PP
6F4765, Bayer) for tolerances by Gustafson, Incorporated, PO Box
660065, Dallas, Texas 75255-0065; and Bayer Corporation, 8400 Hawthorn
Road, PO Box 4913, Kansas City, MO 64120-0013. These notices included
summaries of the petitions prepared by Gustafson, Incorporated, and
Bayer Corporation, the registrants. There were no comments received in
response to the notices of filing. The petitions requested that 40 CFR
180.472(a) and (d) be amended by establishing tolerances for combined
residues of the insecticide imidacloprid (1-[(6-chloro-3-pyridinyl)
methyl]-N-nitro-2-imidazolidinimine) and its metabolites containing the
6-chloropyridinyl moiety, all expressed as (1-[(6-chloro-3-pyridinyl)
methyl]-N-nitro-2-imidazolidinimine), in or on sugar beets (tops) at
0.5, roots at 0.05, molasses at 0.3 parts per million (ppm), barley
(grain) at 0.05, straw at 0.5, hay at 0.5 ppm, wheat (grain) at 0.05,
forage at 7.0, straw at 0.5, hay at 0.5 ppm 40 CFR 180.472(a); and
cereal grains crop group - grain at 0.05, forage at 2.0, straw at 3.0,
hay at 6.0, stover at 0.3 ppm, sweet corn (kernel plus cob with husk
removed) at 0.05, safflower - seed at 0.05, meal at 0.5, legume
vegetable crop group - seed at 0.3, foliage at 2.5, soybean meal at 0.5
ppm (inadvertent or indirect residues, 40 CFR 180.472(d)).
I. Risk Assessment and Statutory Findings
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable
certainty that no harm will result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information.'' This
includes exposure through drinking water and in residential settings,
but does not include occupational exposure. Section 408(b)(2)(C)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to ``ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue. . . .''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the Final Rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
II. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of
imidacloprid and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for tolerances for the combined
residues of imidacloprid and its metabolites containing the 6-
chloropyridinyl moiety in or on sugar beets (tops) at 0.5, roots at
0.05, molasses at 0.3 parts per million (ppm), barley (grain) at 0.05,
straw at 0.5, hay at 0.5 ppm, wheat grain at 0.05, forage at 7.0, straw
at 0.5, hay at 0.5 ppm (40 CFR 180.472(a); and cereal grains crop group
- grain at 0.05, forage at 2.0, straw at 3.0, hay at 6.0, stover at 0.3
ppm, sweet corn (kernel plus cob with husk removed) at 0.05, safflower
- seed at 0.05, meal at 0.5, legume vegetable crop group - seed at 0.3,
foliage at 2.5, soybean meal at 0.5 ppm (40 CFR.180.472(d)). EPA's
assessment of the dietary exposures and risks associated with
establishing the tolerances follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by imidacloprid are
discussed below.
1. Acute toxicity. The following table contains a summary of the
acute toxicity data for technical imidacloprid.
----------------------------------------------------------------------------------------------------------------
Guideline Number Study Type MRIDs Nos. Results Toxicity Category
----------------------------------------------------------------------------------------------------------------
81-1 Acute Oral 42055331 LD50 = 424 mg/kg II
(M)
> 450 mg/kg (F)
----------------------------------------------------------------------------------------------------------------
81-2 Acute Dermal 42055332 LD50 >5,000 mg/kg IV
----------------------------------------------------------------------------------------------------------------
81-3 Acute Inhalation 42256317 LC50 > 5.33 mg/L IV
----------------------------------------------------------------------------------------------------------------
81-4 Primary Eye 42055334 Non-irritant IV
Irritation
----------------------------------------------------------------------------------------------------------------
81-5 Primary Skin 42055335 Non-irritant IV
Irritation
----------------------------------------------------------------------------------------------------------------
81-6 Dermal 42055336 Non-sensitizer NA
Sensitization
----------------------------------------------------------------------------------------------------------------
81-8 Acute Neurotoxicity 41317301 NOAEL = Not NA
43285801 established
LOEL = 42 mg/kg
bwt/day
----------------------------------------------------------------------------------------------------------------
The following table contains a summary of the acute toxicity of the
end-use product (40.7% formulation) for imidacloprid (Gaucho 480F, EPA
Reg. No. 7501-155).
[[Page 49839]]
----------------------------------------------------------------------------------------------------------------
Guideline Number Study Type MRIDs Nos. Results Toxicity Category
----------------------------------------------------------------------------------------------------------------
81-1 Acute Oral/Rat 42857703 LD50 = 4687 mg/kg III
(M)
4067 mg/kg (F)
----------------------------------------------------------------------------------------------------------------
81-2 Acute Dermal/Rat 42857703 LD50 >5,050 mg/kg IV
----------------------------------------------------------------------------------------------------------------
81-3 Acute Inhalation/ 42256326 LC50 = 2.11 mg/L IV
Rat (M&F)
----------------------------------------------------------------------------------------------------------------
81-4 Primary Eye 42857705 Irritation score: IV
Irritation/Rabbit 0.7 (1 hr.); 0.1
(24 hr.)
0.0 (48 hr.); 0.0
(72 hr.)
----------------------------------------------------------------------------------------------------------------
81-5 Primary Dermal 42256328 PIS: 0.0 (non- IV
Irritation/Rabbit irritating)
----------------------------------------------------------------------------------------------------------------
81-6 Dermal 42857707 Not a sensitizer NA
Sensitization/
Guinea Pig
----------------------------------------------------------------------------------------------------------------
2. 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 milligrams/kilograms (mg/
kg) body weight/day (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 no observable adverse effect level (NOAEL) was
>1,000 mg/kg bwt/day; a lowest observable effect level (LOEL) was not
established (MRID No. 42256329).
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 LOEL
was 1,000 ppm (63.3 and 69.3 mg/kg bwt/day in males and females,
respectively) (MRID No. 43286401).
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 (MRID No. 422730-01).
3. 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 LOEL 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 to the lack of toxicity at 1,250 ppm, a LOEL 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 LOEL (MRID No. 42273002).
4. Carcinogenicity. In a combined chronic toxicity/carcinogenicity
study, groups of Bor WISW rats (50/sex/dose) received imidacloprid
(95.3%) at 0, 100, 300 or 900 ppm (0, 5.7, 16.9 or 51.3 mg/kg bwt/day
in males and 0, 7.6, 24.9, or 73 mg/kg bwt/day in females,
respectively) for 104 weeks. In another study, rats of the same strain
(50/sex) received imidacloprid at 0 or 1,800 ppm (0, 102.6, and 143.7
mg/kg bwt/day in males and females, respectively) for 104 weeks. For
chronic toxicity, the NOAEL was 100 ppm (5.7 mg/kg bwt/day) and the
LOEL was 300 ppm (16.9 mg/kg bwt/day) based on decreased body weight
gains in females and increased thyroid lesions in males. There was no
evidence of carcinogenicity in either sex (MRID No. 42256331 and
42256332).
In carcinogenicity study groups of B6C3F1 mice (50/sex/dose) were
fed diets containing imidacloprid (95%) at 0, 100, 330 or 1,000 ppm (0,
20, 66, or 208 mg/kg bwt/day in males and 0, 30, 104 or 274 mg/kg bwt/
day in females, respectively) for 2 years. In a supplementary study
conducted to evaluate the adequacy of the high dose tested in the main
study, the same strain of mice (50/sex) received 0 or 2,000 ppm (414
and 424 mg/kg bwt/day in males and females, respectively) for the same
time period. For chronic toxicity, the NOAEL was 1,000 ppm (208 mg/kg
bwt/day). The LOEL was 2,000 ppm (414 mg/kg bwt/day) based on decreased
body weight gain, food consumption, and water consumption. There was no
evidence of carcinogenicity in either sex (MRID No. 42256335 and
42256336).
5. 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 LOEL was 10 mg/kg bwt/day
(LDT) based on decreased body weight gain; a NOAEL was not established.
For developmental toxicity, the NOAEL was 30 mg/kg bwt/day and the LOEL
was 100 mg/kg bwt/day based on increased wavy ribs (MRID No. 42256338).
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 LOEL 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 LOEL was 72 mg/kg bwt/day based on
decreased fetal body weight, increased resorptions, and increased
skeletal abnormalities (MRID No. 42256339).
[[Page 49840]]
6. Reproductive toxicity. 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)
(MRID No. 42256340, Doc. No. 010537). For parental/systemic/
reproductive toxicity, the NOAEL was 250 ppm (18.3 mg/kg bwt/day) and
the LOEL 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
EPA/OPP/HED Hazard Identification Assessment Review Committee (HIARC)
recommended that the Data Evaluation Record should be revised to
indicate the parental/systemic/reproductive NOAEL and LOEL to be 250
and 700 ppm, respectively, based upon the body weight decrements
observed in both sexes in both generations.
7. Mutagenicity. As shown below, mutagenicity studies have
demonstrated that imidacloprid is non-mutagenic both in vivo and in
vitro.
------------------------------------------------------------------------
Assay MRIDs Nos. Results
------------------------------------------------------------------------
Ames-Salmonella 42256363 Negative up to
5,500 g/
plate
------------------------------------------------------------------------
Recombination assay - yeast 42256353 Negative for
crossing-over in
yeast up to
10,000 g
------------------------------------------------------------------------
Chromosomal aberration - in vivo 42256344 Negative for
chromosome
breakage up to
2,000 g/
mL
------------------------------------------------------------------------
Chromosomal aberration - in 42256345 Positive at 500
vitro g/mL -S9
and 1,300 g/mL +S9, both
toxic doses
------------------------------------------------------------------------
Sister Chromatid assay - in vivo 42256346 Negative up to
2,000 g/
mL
------------------------------------------------------------------------
Cytogenetics -CHO cells - in 42256342 Negative for
vitro inducing forward
mutation in CHO
(mammalian) cells
treated up to
1,222 g/
mL
------------------------------------------------------------------------
Micronucleus - mouse 42256366 Negative up to
(toxic) 50 mg/kg
(ip)
------------------------------------------------------------------------
DNA repair test 42256353 Negative for
crossing-over in
yeast up to
10,000 g
------------------------------------------------------------------------
HGPRT assay - CHO 42256365 Negative up to
2,000 g/
mL
------------------------------------------------------------------------
8. Dermal absorption. No dermal absorption studies are available.
However, this is not a concern since occupational and residential risk
assessments are not required for dermal exposure due to the lack of
dermal or systemic toxicity (following single or repeated dermal
application of imidacloprid to laboratory animals).
9. Neurotoxicity. In an acute neurotoxicity study, groups of
Sprague-Dawley rats (18/sex/dose) were given a single oral
administration of imidacloprid (97.6%) in 0.5% methyl cellulose with
0.4% Tween 80 in deionized water at 0, 42, 151, or 307 mg/kg.
Parameters evaluated included: clinical pathology (6/sex/dose);
Functional Observation Battery (FOB) measurements (12/sex/dose); and
neuropathology (6/sex/dose). FOB measurements were made approximately
90 minutes post dosing, and on days 7 and 14. Motor activity
measurements were made at approximately 2.5 hours post dosing.
At 307 mg/kg bwt/day, 4/18 males and 10/18 females died and both
sexes of rats at this dose exhibited decreased numbers of rears, grip
strength (forelimb and hindlimb) and response to stimuli (auditory,
touch, or tail pinch) as well as increased gait abnormalities, righting
reflex impairments and body temperatures. These symptoms regressed by
day 5. At 151 mg/kg bwt/day, cage side FOB assessments revealed tremors
in one male and one female and red nasal staining in one male. On the
day of dosing, a dose-related decrease in total session motor activity
was observed in males at 151 mg/kg bwt/day (25% decrease) and 307 mg/kg
bwt/day (73%) and in females at all dose levels with the decreases (25,
48, and 81%, respectively at 42, 151, and 307 mg/kg bwt/day) reaching
statistical significance (p <0.05) at="" 151="" and="" 307="" mg/kg="" bwt/day="" dose="" levels.="" decreases="" in="" motor="" activity="" were="" seen="" at="" all="" time="" intervals.="" total="" session="" locomotor="" activity="" was="" also="" decreased="" to="" about="" the="" same="" percentage="" difference="" but="" statistical="" significance="" was="" not="" reported.="" on="" days="" 7="" and="" 14,="" decreases="" (not="" statistically="" significant)="" were="" still="" observed="" in="" motor="" and="" locomotor="" activity="" in="" surviving="" high-dose="" males.="" the="" loel="" was="" 42="" mg/kg="" based="" on="" the="" decrease="" in="" motor="" and="" locomotor="" activities="" observed="" in="" females;="" a="" noael="" was="" not="" established="" (mrid="" no.="" 41317031="" and="" 43285801).="" 10.="" other-toxicological="" considerations.="" epa="" is="" requiring="" a="" developmental="" neurotoxicity="" study="" (guideline="" no.="" 83-6)="" for="" imidacloprid.="" the="" following="" information="" was="" considered="" in="" the="" weight-="" of-evidence="" evaluation:="" i.="" imidacloprid="" is="" a="" neurotoxic="" chemical.="" evidence="" of="" functional="" neurotoxicity="" was="" seen="" in="" the="" acute="" neurotoxicity="" study="" where="" a="" single="" oral="" dose="" caused="" a="" dose-related="" decrease="" in="" motor="" activity="" in="" all="" dosed="" females,="" including="" a="" 25%="" decrease="" at="" the="" lowest="" dose="" tested="" (42="" mg/kg="" bwt/day).="" ii.="" imidacloprid="" is="" a="" nicotine="" analog="" and="" is="" expected="" to="" act="" as="" a="" nicotinic="" agonist.="" iii.="" with="" this="" class="" of="" chemical,="" there="" is="" no="" readily="" available="" biomarker="" (e.g.,="" cholinesterase="" inhibition)="" for="" assessment="" of="" subtle="" neurotoxic="" effects.="" iv.="" in="" the="" 1993="" 2-year="" chronic="" study="" in="" rats,="" significant="" alterations="" of="" brain="" weight="" were="" noted="" in="" males="" and="" females="" at="" 900="" ppm="" (51.3="" and="" 73="" mg/kg="" bwt/day="" in="" males="" and="" females,="" respectively).="" v.="" there="" has="" been="" no="" assessment="" of="" the="" delayed="" neurotoxicity="" study="" in="" the="" hen.="" vi.="" a="" review="" of="" the="" literature="" suggests="" that="" nicotine="" causes="" developmental="" toxicity,="" including="" functional="" deficits,="" in="" animals="" and/="" or="" humans="" exposed="" in="" utero.="" 11.="" metabolism.="" the="" metabolism="" of="" ntn="" 33893="" (imidacloprid)="" in="" rats="" was="" reported="" in="" seven="" studies="" (85-1),="" and="" found="" to="" be="" core="" minimum.="" they="" are:="" i.="">14C] Imidacloprid: Metabolism Part of the
General
[[Page 49841]]
Metabolism Study in the Rat (MRID No. 42256354).
ii. [14C]-NTN 33893: Biokinetic Part of the General
Metabolism Study in the Rat (MRID No. 42256356).
iii. [Imidazolidine-4,5-14C] Imidacloprid: Investigation
of the Biokinetic Behavior and Metabolism in the Rat (MRID No.
42256357).
iv. Imidacloprid - WAK 3839: Comparison of the Biokinetic Behavior
and Metabolism in the Rat Following Single Oral Dosage and
Investigation of the Metabolism after Chronic Feeding of Imidacloprid
to Rats and Mice (MRID No. 42256373).
v. A Liquid Chromatographic Method for the Determination of NTN
33893 in Aqueous Dose Mixtures (MRID No. 42256359).
vi. A Liquid Chromatographic Method for the Determination of NTN
33893 in Inhalation Chamber Atmospheres (MRID No. 42256358).
vii. [14C]-NTN 33893: Investigations on the Distribution
of Total Radioactivity in the Rat by Whole-Body Autoradiography (MRID
No. 42256355).
These data show 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.
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.
B. Toxicological Endpoints
1. Acute toxicity. The endpoint selected for acute dietary risk
assessment is based on neurotoxicity characterized by decreases in
motor or locomotor activity in female rats at 42 mg/kg bwt/day (LOEL)
in an acute neurotoxicity study (MRID No. 41370301 and 43285801). A
NOAEL was not established in this study.
Although developmental toxicity studies showed no increases in
sensitivity in fetuses as compared to maternal animals following in
utero exposures in rats and rabbits, and no increased sensitivity in
pups as compared to adults and offspring in the two generation
reproductive toxicity study in rats, and the toxicology data base is
complete with respect to core requirements, the Agency determined that
an acceptable acute dietary exposure (food plus water) of 33.3% or less
of the acute reference dose (RfD) for all population subgroups is
required based on the following weight-of-the-evidence considerations:
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.
Conventionally, when a LOEL from the critical study is used for
risk assessment, an additional UF will be applied. For acute risk
assessment with imidacloprid, however, the Agency determined that the
3x factor used for FQPA (as discussed under section II.E. of this
unit), is adequate to cover the use of the LOEL as well because of the
low confidence in the endpoint based on the minimal nature of the
effect (decreased motor activity only in females), the fact that this
effect was seen in adult rats, and because the same effect was not seen
in the subchronic toxicity study following repeated doses.
2. Short - and intermediate-term toxicity. No dermal or systemic
toxicity was seen in a 21-day dermal toxicity study in rabbits
following repeated dermal applications of imidacloprid at 1,000 mg/kg
bwt/day (limit-dose) for 3 weeks. In addition, an inhalation endpoint
has not been established for imidacloprid. In a 28-day rat inhalation
study in which rats were exposed 6 hours/day, 5 days/week, the NOAEL
was 5.5 mg/m3. Imidacloprid also has a relatively low vapor
pressure (6.9 x 10-9 torr). Since available data show no
potential for dermal or inhalation toxicity from short- and
intermediate-term exposure to imidacloprid, a risk assessment is not
required.
3. Chronic toxicity. EPA has established the RfD for imidacloprid
at 0.057 mg/kg/day. This RfD is based on the results of a combined
chronic toxicity/ carcinogenicity study, in which groups of Bor WISW
rats (50/sex/dose) received imidacloprid (95.3%) at 0, 100, 300, or 900
ppm (0, 5.7, 16.9 or 51.3 mg/kg bwt/day in males and 0, 7.6, 24.9, or
73 mg/kg bwt/day in females, respectively) for 104 weeks. For chronic
toxicity, the NOAEL was 100 ppm (5.7 mg/kg bwt/day in males and 7.6 mg/
kg bwt/day in females) and the LOEL was 300 ppm (16.9 mg/kg bwt/day in
males and 24.9 mg/kg bwt/day in females) based on decreased body weight
gains in females and increased thyroid lesions in males. Organ weight
changes were observed in both sexes of rats at a dose of 900 ppm. There
was no evidence of carcinogenicity in either sex. Dose/endpoint for
establishing the RfD: NOAEL = 5.7 mg/kg bwt/day based on decreased body
weight gains in females and increased number of thyroid lesions in
males at 16.9 mg/kg bwt/day (LOEL). This is the endpoint selected for
chronic dietary risk assessment.
Uncertainty Factor (UF): 10x for inter-species variation plus 10x for
intra-species variation
Chronic RfD: The RfD is calculated as follows: Chronic RfD = NOAEL
UF = 5.7 mg/kg bwt/day 100 = 0.057 mg/kg bwt/
day
The Agency determined that the additional uncertainty factor (UF)
for FQPA (reduced to 3x as discussed under Units II.B.1. and II.E. of
this preamble) applies to all population subgroups and also applies to
both acute and chronic risk. Application of the additional 3x safety
factor for enhanced susceptibility of infants and children to the
Chronic RfD results in an acceptable chronic dietary exposure (food
plus water) of 33.3% or less of the Chronic RfD for all population
subgroups.
4. Carcinogenicity. Imidacloprid has been classified as a Group E
chemical,
[[Page 49842]]
no evidence of carcinogenicity in humans. A cancer risk assesment is
not required.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.472) for the combined residues of imidacloprid and its
metabolites containing the 6-chloropyridinyl moiety in or on a variety
of raw agricultural commodities and meat at 0.3 ppm, milk 0.1 ppm,
poultry 0.05 ppm, and egg 0.02 ppm. Risk assessments were conducted by
EPA to assess dietary exposures and risks from imidacloprid as follows:
i. Acute exposure and risk. Acute dietary 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 one day or single exposure. As previously stated, the endpoint
selected for assessment of acute dietary risk is 42 mg/kg bwt/day
(LOEL). The UFs are 10x for inter-, 10x for intra-species variations
and 3x for FQPA. Application of the 3X safety factor for enhanced
susceptibility of infants and children to the acute RfD results in an
acceptable acute dietary exposure (food plus water) of 33.3% or less of
the acute RfD for all population subgroups. An acute dietary risk
assessment is required for all population subgroups.
This acute dietary (food) risk assessment used the Theoretical
Maximum Residue Contribution (TMRC) which assumes tolerance level
residues and 100% crop-treated. The DRES System was used for this acute
dietary exposure analysis. The analysis evaluates individual food
consumption as reported by respondents in the USDA 1977-78 Nationwide
Food Consumption Survey (NFCS) and accumulates exposure to the chemical
for each commodity. Resulting exposure values and percent of the acute
RfD utilized are shown below.
------------------------------------------------------------------------
Acute Dietary (Food Only) Exposure and Risk for Imidacloprid
-------------------------------------------------------------------------
Exposure @ 99th
Population Subgroup Percentile (mg/kg Percent Acute RfD
bwt/day)
------------------------------------------------------------------------
U.S. Population (48 states) 0.050 12%
------------------------------------------------------------------------
Infants (< 1="" yr)="" 0.10="" 24%="" ------------------------------------------------------------------------="" children="" (1-6="" yrs)="" 0.10="" 24%="" ------------------------------------------------------------------------="" females="" (13+="" yrs)="" 0.040="" 9.5%="" ------------------------------------------------------------------------="" males="" (13+="" yrs)="" 0.050="" 12%="" ------------------------------------------------------------------------="" values="" for="" the="" 99th="" percentile="" are="" considered="" to="" be="" conservative="" as="" epa="" policy="" dictates="" exposure="" estimates="" from="" as="" low="" as="" the="" 95th="" percentile="" may="" be="" utilized="" for="" risk="" estimates="" from="" acute="" dres="" runs="" not="" using="" monte="" carlo="" analysis.="" thus,="" these="" results="" should="" be="" viewed="" as="" a="" very="" conservative="" risk="" estimate;="" refinement="" using="" anticipated="" residue="" values="" and="" percent="" crop-treated="" information="" in="" conjunction="" with="" monte="" carlo="" analysis="" would="" result="" in="" a="" lower="" estimate="" of="" acute="" dietary="" exposure.="" ii.="" chronic="" exposure="" and="" risk.="" the="" chronic="" dietary="" exposure="" analysis="" from="" food="" sources="" was="" conducted="" using="" the="" reference="" dose="" (chronic="" rfd)="" of="" 0.057="" mg/kg="" bwt/day.="" the="" fqpa="" safety="" factor="" for="" enhanced="" sensitivity="" of="" infants="" and="" children="" was="" reduced="" to="" 3x.="" the="" fqpa="" factor="" was="" applied="" in="" the="" risk="" assessment="" for="" all="" population="" subgroups.="" application="" of="" the="" 3x="" safety="" factor="" for="" enhanced="" susceptibility="" of="" infants="" and="" children="" to="" the="" chronic="" rfd="" results="" in="" an="" acceptable="" chronic="" dietary="" exposure="" (food="" plus="" water)="" of="" 33.3%="" or="" less="" of="" the="" chronic="" rfd="" for="" all="" population="" subgroups.="" a="" tolerance="" is="" established="" for="" residues="" of="" imidacloprid="" and="" its="" metabolites="" containing="" the="" 6-chloropyridinyl="" moiety,="" all="" expressed="" as="" parent,="" in="" or="" on="" canola="" seed="" at="" 0.05="" ppm.="" canola="" seed="" per="" se="" is="" not="" a="" human="" food="" item.="" canola="" seed="" is="" processed="" into="" canola="" oil="" which="" is="" consumed="" by="" humans.="" because="" canola="" is="" not="" listed="" as="" a="" commodity="" in="" dres,="" epa="" has="" estimated="" the="" dietary="" exposure="" from="" imidacloprid="" treated="" canola="" seed="" in="" the="" following="" manner:="" consumption="" (g/kg/day)="" x="" residue="" (mg/kg)="Exposure" (mg/kg="" bwt/day)="" the="" consumption="" value="" for="" canola="" was="" taken="" as="" the="" u.s.="" production="" volume="" (877="" million="" lbs="" or="" 3.98="" x="">11 g) divided by the
U.S. population in the 1977-1978 USDA Food Consumption Survey (240
million) to get grams of canola consumed per year. Further division was
done to estimate consumption per day for an average person (body weight
58.9 kg) to get consumption per person per day. Tolerance level
residues and 100% crop treated were assumed. The estimated exposure
resulting from the established imidacloprid tolerance on canola (0.05
ppm) is 3.86 x 10-6 mg/kg bwt/day. This exposure represents
<1.0% of="" the="" rfd.="" epa="" concludes="" the="" dietary="" exposure="" from="" the="" imidacloprid="" tolerance="" on="" canola="" is="" not="" significant.="" this="" approach="" to="" estimating="" the="" exposure="" due="" to="" consumption="" of="" imidacloprid="" treated="" canola="" results="" in="" a="" conservative="" exposure="" assessment.="" epa="" notes="" that="" the="" consumption="" of="" corn="" oil="" by="" the="" general="" us="" population="" in="" the="" 1977-1978="" usda="" food="" consumption="" survey="" was="" only="" 0.022="" g/kg="" bwt/day.="" the="" consumption="" estimate="" for="" canola="" is="" approximately="" 3.5="" times="" this="" value.="" in="" conducting="" this="" chronic="" dietary="" (food)="" risk="" assessment,="" epa="" used:="" (1)="" tolerance="" level="" residues="" for="" the="" proposed="" tolerances="" of="" these="" petitions="" and="" all="" other="" commodities="" with="" published,="" pending,="" permanent="" or="" time-limited,="" imidacloprid="" tolerances;="" and="" (2)="" percent="" crop-treated="" information="" on="" some="" of="" these="" crops.="" thus,="" this="" risk="" assessment="" should="" be="" viewed="" as="" partially="" refined.="" further="" refinement="" using="" anticipated="" residue="" values="" and="" additional="" percent="" crop="" treated="" information="" would="" result="" in="" a="" lower="" estimate="" of="" chronic="" dietary="" exposure.="" the="" dres="" system="" was="" used="" for="" this="" chronic="" dietary="" exposure="" analysis.="" the="" analysis="" evaluates="" individual="" food="" consumption="" as="" reported="" by="" respondents="" in="" the="" usda="" 1977-1978="" nationwide="" food="" consumption="" survey="" (nfcs)="" and="" accumulates="" exposure="" to="" the="" chemical="" for="" each="" commodity.="" the="" racs="" (raw="" agricultural="" commodities)="" and="" tolerances,="" used="" in="" the="" dietary="" risk="" assessment,="" were="" derived="" from="" 40="" cfr="" 180.472="" and="" epa's="" tolerance="" index="" system.="" the="" following="" table="" summarizes="" the="" estimated="" dietary="" exposures="" for="" the="" u.s.="" population,="" those="" population="" subgroups="" that="" include="" infants="" and="" children,="" and="" [[page="" 49843]]="" all="" population="" subgroups="" with="" risk="" estimates="" above="" that="" of="" the="" u.s.="" population.="" ------------------------------------------------------------------------="" chronic="" dietary="" exposure="" (food="" only)="" and="" risk="" for="" imidacloprid="" -------------------------------------------------------------------------="" exposure="" (mg/kg="" percent="" chronic="" subgroup="" bwt/day)="" rfd="" ------------------------------------------------------------------------="" u.s.="" population="" (48="" states)="" 0.0039="" 6.8%="" ------------------------------------------------------------------------="" nursing="" infants="">< 1="" year="" old)="" 0.0032="" 5.6%="" ------------------------------------------------------------------------="" non-nursing="" infants=""><1 year="" 0.011="" 19%="" old)="" ------------------------------------------------------------------------="" children="" (1="" to="" 6="" years="" old)="" 0.0081="" 14%="" ------------------------------------------------------------------------="" children="" (7="" to="" 12="" years="" old)="" 0.0057="" 10%="" ------------------------------------------------------------------------="" u.s.="" population="" -="" fall="" season="" 0.0040="" 7.0%="" ------------------------------------------------------------------------="" u.s.="" population="" winter="" season="" 0.0040="" 7.0%="" ------------------------------------------------------------------------="" northeast="" region="" 0.0040="" 7.0%="" ------------------------------------------------------------------------="" western="" region="" 0.0041="" 7.2%="" ------------------------------------------------------------------------="" hispanics="" 0.0043="" 7.5%="" ------------------------------------------------------------------------="" non-hispanic="" others="" 0.0042="" 7.4%="" ------------------------------------------------------------------------="" section="" 408(b)(2)(f)="" states="" that="" the="" agency="" may="" use="" data="" on="" the="" actual="" percent="" of="" food="" treated="" for="" assessing="" chronic="" dietary="" risk="" only="" if="" the="" agency="" can="" make="" the="" following="" findings:="" (1)="" that="" the="" data="" used="" are="" reliable="" and="" provide="" a="" valid="" basis="" to="" show="" what="" percentage="" of="" the="" food="" derived="" from="" such="" crop="" is="" likely="" to="" contain="" such="" pesticide="" residue;="" (2)="" that="" the="" exposure="" estimate="" does="" not="" underestimate="" exposure="" for="" any="" significant="" subpopulation="" group;="" and="" (3)="" if="" data="" are="" available="" on="" pesticide="" use="" and="" food="" consumption="" in="" a="" particular="" area,="" the="" exposure="" estimate="" does="" not="" understate="" exposure="" for="" the="" population="" in="" such="" area.="" in="" addition,="" the="" agency="" must="" provide="" for="" periodic="" evaluation="" of="" any="" estimates="" used.="" to="" provide="" for="" the="" periodic="" evaluation="" of="" the="" estimate="" of="" percent="" crop="" treated="" as="" required="" by="" the="" section="" 408(b)(2)(f),="" epa="" may="" require="" registrants="" to="" submit="" data="" on="" percent="" crop="" treated.="" the="" agency="" used="" percent="" crop="" treated="" (pct)="" information="" as="" follows.="" a="" routine="" chronic="" dietary="" exposure="" analysis="" for="" imidacloprid="" was="" based="" on="" likely="" maximum="" percent="" of="" crop="" treated="" as="" follows:="" 6%="" grapefruits,="" 3%="" oranges,="" 13%="" other="" citrus,="" 19%="" apples,="" 2%="" pears,="" 11%="" grapes,="" 30%="" eggplants/peppers,="" 32%="" head="" lettuce,="" 21%="" cole="" crops,="" 15%="" melons,="" 10%="" tomatoes,="" 6%="" cotton.="" the="" agency="" believes="" that="" the="" three="" conditions="" listed="" above="" have="" been="" met.="" with="" respect="" to="" finding="" (1),="" epa="" finds="" that="" the="" pct="" information="" described="" above="" for="" imidacloprid="" is="" reliable="" and="" has="" a="" valid="" basis,="" the="" agency="" has="" utilized="" the="" latest="" statistical="" data="" from="" rff="" (resources="" for="" the="" future),="" doane,="" and="" usda,="" the="" best="" available="" sources="" for="" such="" information.="" concerning="" findings="" (2)="" and="" (3),="" regional="" consumption="" information="" and="" consumption="" information="" for="" significant="" subpopulations="" is="" taken="" into="" account="" through="" epa's="" computer-based="" model="" for="" evaluating="" the="" exposure="" of="" significant="" subpopulations="" including="" several="" regional="" groups.="" use="" of="" this="" consumption="" information="" in="" epa's="" risk="" assessment="" process="" ensures="" that="" epa's="" exposure="" estimate="" does="" not="" understate="" exposure="" for="" any="" significant="" subpopulation="" group="" and="" allows="" the="" agency="" to="" be="" reasonably="" certain="" that="" no="" regional="" population="" is="" exposed="" to="" residue="" levels="" higher="" than="" those="" estimated="" by="" the="" agency.="" other="" than="" data="" available="" through="" national="" food="" consumption="" surveys,="" epa="" does="" not="" have="" available="" information="" on="" the="" consumption="" of="" food="" bearing="" imidacloprid="" in="" a="" particular="" area.="" 2.="" from="" drinking="" water.="" there="" are="" no="" maximum="" contaminant="" levels="" (mcl)="" or="" health="" advisory="" (ha)="" levels="" established="" for="" residues="" of="" imidacloprid="" in="" drinking="" water.="" this="" information="" was="" furnished="" by="" the="" epa="" safe="" drinking="" water="" hotline="" (1-800-426-4791)="" on="" june="" 16,="" 1998.="" information="" in="" epa's="" pesticide="" environmental="" fate="" one="" line="" summary="" data="" base="" (last="" update="" may="" 6,="" 1997)="" suggests="" that="" imidacloprid="" is="" persistent="" and="" mobile.="" epa's="" ``pesticides="" in="" ground="" water="" database''="" (epa="" 734-12-92-001,="" 9/92)="" has="" no="" entry="" for="" imidacloprid.="" i.="" acute="" exposure="" and="" risk--a.="" acute="" exposure.="" estimated="" maximum="" concentrations="" of="" imidacloprid="" in="" surface="" and="" ground="" water="" are="" 50.9="" and="" 0.605="" ppb,="" respectively.="" epa="" used="" przm1="" (pesticide="" root="" zone="" model="" -="" simulates="" the="" transport="" of="" a="" pesticide="" off="" the="" agricultural="" field)="" and="" exams="" (exposure="" analysis="" modeling="" system="" -="" simulates="" fate="" and="" transport="" of="" a="" pesticide="" in="" surface="" water)="" models="" to="" estimate="" concentrations="" of="" imidacloprid="" residues="" in="" surface="" water.="" it="" should="" be="" noted="" that="" przm1/exams="" models="" were="" designed="" for="" use="" in="" ecological="" risk="" assessment.="" they="" are="" not="" ideal="" tools="" for="" use="" in="" drinking="" water="" risk="" assessment.="" przm1/exams="" could="" overestimate="" actual="" drinking="" water="" concentrations.="" thus,="" these="" models="" should="" be="" considered="" a="" screening="" tool.="" epa="" used="" the="" sci-grow="" (screening="" concentration="" in="" ground="" water)="" model="" to="" estimate="" the="" concentration="" of="" imidacloprid="" residues="" in="" ground="" water.="" sci-grow="" is="" a="" prototype="" model="" for="" estimating="" ``worst="" case''="" ground="" water="" concentrations="" of="" pesticides.="" sci-grow="" is="" biased="" in="" that="" studies="" where="" the="" pesticide="" is="" not="" detected="" in="" ground="" water="" are="" not="" included="" in="" the="" data="" set.="" thus,="" it="" is="" not="" expected="" that="" sci-grow="" estimates="" would="" be="" exceeded.="" b.="" acute="" risk.="" epa="" has="" calculated="" drinking="" water="" levels="" of="" concern="" (dwloc's)="" for="" acute="" exposure="" to="" imidacloprid="" in="" surface="" and="" ground="" [[page="" 49844]]="" water="" for="" various="" population="" subgroups.="" the="" dwloc's="" for="" acute="" exposure="" to="" imidacloprid="" are="" summarized="" below.="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" drinking="" water="" levels="" of="" concern="" for="" acute="" exposure="" to="" imidacloprid="" ---------------------------------------------------------------------------------------------------------------------------------------------------------="" dietary="">1 (mg/ Max. Exposure from Daily Water
Population Subgroup kg bwt/day) Water (mg/kg bwt/day) Bodyweight (kg) Consumption (Liters) DWLOC (g/L)
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Population (48 States) 0.050 0.090 70 2 3,200
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (13+ years) 0.040 0.10 60 2 3,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children (1 - 6 years) 0.010 0.13 10 1 1,300
--------------------------------------------------------------------------------------------------------------------------------------------------------
199th percentile
To calculate the DWLOC relative to an acute toxicity endpoint, the
acute dietary food exposure (from DRES) was subtracted from one-third
the Acute RfD to obtain the acceptable acute exposure to imidacloprid
in drinking water. The value of one-third the Acute RfD was utilized to
account for the FQPA Safety Factor of 3x. DWLOCs were then calculated
using default body weights and drinking water consumption figures.
ii. Short-term exposure and risk--a. Short-term exposure. Estimated
maximum concentrations of imidacloprid in surface and ground water are
50.9 and 0.605 g/mL, respectively. EPA utilized PRZM1 and
EXAMS to generate these estimates. Descriptions of these models are
above.
b. Short-term risk. EPA has calculated a drinking water level of
concern (DWLOC) for short-term exposure to imidacloprid in surface and
ground water for the population subgroup children, 1 to 6 years old.
This DWLOC is for short-term exposure to imidacloprid from home garden
and turf uses. A DWLOC for short-term exposure from imidacloprid pet
uses was not determined as the exposure level from the home garden and
turf uses is higher than that of the pet uses. Thus, the DWLOC for the
imidacloprid pet uses will be higher than that of the home garden and
turf uses. The DWLOC for short-term exposure to imidacloprid is
summarized below.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Drinking Water Levels of Concern for Short-Term Exposure to Imidacloprid
---------------------------------------------------------------------------------------------------------------------------------------------------------
Total Exposure1 (mg/kg Max. Exposure from Daily Water
Population Subgroup bwt/day) Water (mg/kg bwt/day) Bodyweight (kg) Consumption (Liters) DWLOC (g/L)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children (1 - 6 years) 0.080 0.060 10 1 600
--------------------------------------------------------------------------------------------------------------------------------------------------------
1Total Exposure = sum of exposures from chronic food plus home turf and garden uses.
The DWLOC for short-term exposure to imidacloprid was calculated
relative to the acute RfD which was utilized for estimating risk for
short-term oral exposure to imidacloprid. To calculate the DWLOC for
short-term exposure relative to an acute toxicity endpoint, the sum of
chronic dietary food exposure (from DRES) plus the oral exposure from
imidacloprid home garden and turf uses was subtracted from one-third
the Acute RfD to obtain the acceptable short-term exposure to
imidacloprid in drinking water. The value of one-third the Acute RfD
was utilized to account for the FQPA Safety Factor of 3x. DWLOCs were
then calculated using default body weights and drinking water
consumption figures.
iii. Chronic exposure and risk--a. Chronic exposure. The estimated
average concentration of imidacloprid in surface water (for chronic
exposure) is 19.1 g/mL. An estimated average concentration of
imidacloprid in ground water was not provided. EPA used PRZM1 and EXAMS
models to estimate chronic environmental concentrations of imidacloprid
residues in surface water.
b. Chronic risk. EPA has calculated DWLOCs for chronic (non-cancer)
exposure to imidacloprid in surface and ground water for various
population subgroups. The DWLOC's for chronic exposure to imidacloprid
are summarized below.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Drinking Water Levels of Concern for Chronic Exposure to Imidacloprid
---------------------------------------------------------------------------------------------------------------------------------------------------------
Dietary Exposure (mg/ Max. Exposure from Daily Water
Population Subgroup kg bwt/day) Water (mg/kg bwt/day) Bodyweight (kg) Consumption (Liters) DWLOC (g/L)
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Population (48 States) 0.0039 0.015 70 2 530
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (13+ yrs., pregnant) 0.0036 0.015 60 2 460
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 49845]]
Non-nursing Infants 0.011 0.0080 10 1 80
--------------------------------------------------------------------------------------------------------------------------------------------------------
To calculate the DWLOC for chronic (non-cancer) exposure relative
to a chronic toxicity endpoint, the chronic dietary food exposure (from
DRES) was subtracted from one-third the chronic RfD to obtain the
acceptable chronic (non-cancer) exposure to imidacloprid in drinking
water. The value of one-third of the RfD was utilized to account for
the FQPA Safety Factor of 3x. DWLOCs were then calculated using default
body weights and drinking water consumption figures.
A DWLOC for chronic (cancer) exposure was not calculated as
imidacloprid has been classified as a Group E chemical (no evidence of
carcinogenicity).
3. From non-dietary exposure. Imidacloprid is currently registered
for use on the following residential non-food sites: ornamentals (e.g.,
flowering and foliage plants, ground covers, turf, lawns, et al.),
tobacco, golf courses, walkways, recreational areas, household or
domestic dwellings (indoor/outdoor), and cats/dogs. Available data do
not demonstrate that imidacloprid has either dermal or inhalation
toxicity potential, therefore, non-dietary dermal and inhalation
exposure assessments are not required. Since available data show no
toxicity from short-term exposure via the dermal or inhalation route,
the Agency feels there is no contribution to toxicity from these routes
of exposure, and no increase in aggregate risk is anticipated from this
exposure. However, there is the potential for residential exposure via
incidental non-dietary ingestion from treated lawns and gardens and
incidental non-dietary ingestion by toddlers of pesticide residues on
pets from hand-to-mouth transfer. Therefore, an increase in aggregate
risk is anticipated from residential exposure via incidental non-
dietary ingestion and residential exposure and risk assessments are
required for the use of imidacloprid in/on lawns and gardens and on
pets.
The product Premise, a termiticide, is also registered for
residential use. It may be applied only by Pest Control Operators
(PCOs) and only to inaccessible areas of homes or other buildings;
therefore, oral exposure to children is not expected. There is
potential for inhalation exposure; however, an inhalation endpoint has
not been established and imidacloprid has a low vapor pressure (6.9 x
10-9 torr). Since oral exposure to children is not expected
and the Agency feels there is no contribution to toxicity from the
inhalation route of exposure, no increase in aggregate risk is
anticipated and a residential exposure assessment based upon the
imidacloprid termiticide use is not required.
i. Exposure and risk from incidental non-dietary ingestion from
treated lawns and gardens. A summary of post-application exposure
estimates and risk assessments are summarized in the table below. The
post-application exposure scenarios for toddlers examined include:
Incidental non-dietary ingestion of residues on lawns from
hand-to-mouth transfer.
Ingestion of pesticide-treated turfgrass.
Incidental ingestion of soil from treated gardens.
The calculations and assumptions utilized to determine these
exposures are as per the Draft Standard Operating Procedures for
Residential Exposure Assessments (December 18, 1997).
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Post Application Exposure Estimates and Risk Assessments
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
DFRtb (g/ GRtc (g/ SRtd (g/ ADDe (mg/kg bwt/
Scenario Receptor ARa (lb ai/A) cm2) cm2) g) day) NOAEL (mg/kg/day) MOEf
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Hand-to-mouth for treated lawns Toddler 0.4 0.9 -- -- 0.07 42 640
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Turf-grass Toddler 0.4 -- 0.9 -- 0.0015 42 28,000
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Incidental Soil Ingestion Toddler 0.4 -- -- 3 0.000020 42 2,100,000
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
aAR,Application Rate
bDFRt, Dislodgeable foliar residue (g/cm2)
cGRt, Grass residue (g/cm2)
dSRt, Soil residue (g/g)
eADD, Average daily dose (mg/kg bwt/day) .
fMOE = NOAEL/ ADD (No NOAEL established, LOEL of 42 mg/kg bwt/day used)
ii. Exposure and risk to toddlers from incidental non-dietary
ingestion of pesticide residues on pets from hand-to-mouth transfer.
Advantage 110 Flea Adulticide (EPA Reg. No. 011556-121) is a 5.0 mL
vial that is applied to two locations on the dog (2.5 mL per 1 in 2).
The method for assessing hand-to-mouth transfer in the Draft Standard
Operating Procedures for Residential Exposure Assessments (December 18,
1997) is intended for a complete body dip of the treated animal.
Therefore, a modified approach was applied to estimate oral exposures.
Assumptions and calculations used are as follows:
Assumptions:
On the day of application it may be assumed that 20%
(0.20) of the application rate is retained on the pets as dislodgeable
residue. This value is
[[Page 49846]]
based on the professional judgement and experience of the EPA staff
from the review of company-submitted data and is believed to be an
upper-percentile assumption.
It is assumed that 1% (0.01) of the available residues are
transferred to the individuals who have contact with the treated
animals. This is considered to be a conservative assumption in light of
the very low percentage of the pet's total skin surface being treated.
It should be noted that 10% (0.10) is recommended for complete pet dips
in the Draft Standard Operating Procedures for Residential Exposure
Assessments (December 18, 1997). This is the only deviation from the
standard operating procedures.
It was assumed that 100% of the residue on the hands of
toddlers is ingested. This is considered to be a conservative
assumption.
Post application activities assessed on the same day that
the pesticide is applied since it is assumed that toddlers could
handle/touch pets immediately after application. This is considered a
short-term oral exposure.
Toddlers (age 3 years), used to represent the 1 to 6 year
old age group, are assumed to weigh 15 kg.
5.0 mL of product was used per application (EPA Reg. No.
011556-121). Product contains 9.1% ai. Density of formulation is not
given on label. Density of water was assumed for converting volume in
mL to lb active ingredient (ai).
This product represents high-end exposure among similar
products containing imidacloprid given that it involves the highest
volume of the active ingredient.
Calculations:
The average daily dose (ADD = 0.058 mg/kg bwt/day) was calculated
by multiplying the following: application rate (AR = 436 mg ai/day) x
fraction of ai available on pet (F = 0.2) x fraction of residue
transferred to the skin (T = 0.01), and dividing by bwt (15 kg).
A margin of exposure (MOE) of 720 was calculated by dividing the
NOAEL (42 mg/kg bwt/day) by the ADD (0.058 mg/kg). (NOAEL was not
established, therefore acute dietary LOEL of 42 mg/kg bwt/day was
used).
The estimated MOE is 720 which is greater than the minimum required
MOE of 300. Therefore, exposure via incidental non-dietary ingestion of
imidacloprid residues on pets from hand-to-mouth transfer would not
exceed EPA's level of concern. However, it should be noted that the 20%
used for the fraction of active ingredient available on pet (F) and the
1% used for the fraction of residue transferred to the skin (T) are
estimates made by EPA given a lack of available data. The actual values
may differ. It is recommended that the registrant submit a study to
quantify dislodgeable residues on toddler's hands from pets treated
with these types of products.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether imidacloprid 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,
imidacloprid does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that imidacloprid has a common mechanism of
toxicity with other substances. For information regarding EPA's efforts
to determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the Final Rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk--i. Food. The acute dietary (food) risk assessment
used the TMRC. Resulting exposure values and percent of the acute RfD
utilized are shown below.
------------------------------------------------------------------------
Acute Dietary (Food Only) Exposure and Risk for Imidacloprid
-------------------------------------------------------------------------
Exposure @ 99th
Population Subgroup Percentile (mg/kg Percent Acute RfD
bwt/day)
------------------------------------------------------------------------
U.S. Population (48 states) 0.050 12%
------------------------------------------------------------------------
Infants (< 1="" yr)="" 0.10="" 24%="" ------------------------------------------------------------------------="" children="" (1-6="" yrs)="" 0.10="" 24%="" ------------------------------------------------------------------------="" females="" (13+="" yrs)="" 0.040="" 9.5%="" ------------------------------------------------------------------------="" males="" (13+="" yrs)="" 0.050="" 12%="" ------------------------------------------------------------------------="" for="" imidacloprid,="" it="" was="" determined="" that="" an="" acceptable="" acute="" dietary="" exposure="" (food="" plus="" water)="" of="" 33.3%="" or="" less="" of="" the="" acute="" rfd="" for="" all="" population="" subgroups="" is="" needed="" to="" protect="" the="" safety="" of="" all="" population="" subgroups.="" the="" estimated="" exposures="" for="" all="" population="" subgroups="" at="" the="" 99th="" percentile="" utilize="" less="" than="" 33.3%="" of="" the="" acute="" rfd.="" ii.="" water.="" the="" estimated="" maximum="" concentrations="" of="" imidacloprid="" in="" surface="" and="" ground="" water="" (50.9="" and="" 0.605="">g/mL, respectively)
are less than EPA's levels of concern for imidacloprid in drinking
water (1,300, 3,000 and 3,200 g/mL) as a contribution to acute
exposure. Therefore, taking into account the present uses and uses
proposed in this action, EPA concludes with reasonable certainty that
residues of imidacloprid in drinking water (when considered along with
other sources of acute exposure for which EPA has reliable data) would
not result in unacceptable levels of acute aggregate human health risk
estimates at this time.
EPA bases this determination on a comparison of estimated maximum
concentrations of imidacloprid in surface water to back-calculated
``levels of concern'' for imidacloprid in drinking water. These levels
of concern in drinking water were determined after EPA has considered
all other non-occupational/non-residential human exposures for which it
has reliable data, including all current uses, and uses considered in
this action. The estimates of imidacloprid in surface water are
[[Page 49847]]
derived from water quality models that use conservative assumptions
(health-protective) regarding the pesticide transport from the point of
application to surface and ground water. Because EPA considers the
aggregate risk resulting from multiple exposure pathways associated
with a pesticide's uses, levels of concern in drinking water may vary
as those uses change. If new uses are added in the future, EPA will
reassess the potential impacts of imidacloprid in drinking water as a
part of the acute aggregate risk assessment process.
Despite the potential for imidacloprid exposure from drinking
water, EPA concludes that there is a reasonable certainty that no harm
will result to infants, children, or adults from acute aggregate
exposure to imidacloprid residues.
2. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
exposure (considered to be a background exposure level) plus indoor and
outdoor residential exposure. Since dermal and inhalation exposure
endpoints (short-term) were not identified due to the demonstrated
absence of toxicity, no increase in aggregate risk is anticipated from
dermal and inhalation exposure. Therefore, dermal and inhalation short-
term risk assessments are not required for imidacloprid.
In addition to its food uses, imidacloprid is registered for use on
turf, home gardens and pets. EPA has identified potential short-term
oral exposures to toddlers for these uses. These exposures include the
following scenarios:
Incidental non-dietary ingestion of residues on lawns from
hand-to-mouth transfer.
Ingestion of pesticide-treated turfgrass.
Incidental ingestion of soil from treated gardens.
Incidental ingestion of pesticide residues on pets from
hand-to-mouth transfer.
According to current EPA policy, these exposures are considered to
be short-term oral exposures. EPA does not expect incidental ingestion
of pesticide residues on pets from hand-to-mouth transfer to occur
during the same period as the exposures from the turf and home garden
uses. Thus, we will consider these exposures in separate estimates of
risk. The tables below summarize the short-term aggregate exposures for
imidacloprid from turf and garden uses and from the pet use.
A short-term oral endpoint was not identified for imidacloprid.
According to current EPA policy, if an oral endpoint is needed for
short-term risk assessment (for incorporation of food, water, or oral
hand-to-mouth type exposures into an aggregate risk assessment), the
acute oral endpoint (acute RfD = 0.42 mg/kg bwt/day) will be used to
incorporate the oral component into aggregate risk. Short-term
aggregate exposure is defined by EPA to be average food and water
exposure (chronic exposure) plus residential exposure. The short-term
risk estimates for the population subgroup Children, 1 to 6 years old,
is summarized below. This population subgroup was chosen because it has
the highest chronic food exposure and because toddlers have the highest
exposure from the residential uses.
----------------------------------------------------------------------------------------------------------------
Short-Term Aggregate Exposure and Risk (Includes Turf and Garden Uses of Imidacloprid)
-----------------------------------------------------------------------------------------------------------------
Chronic Food Residential
Population Subgroup Exposure (mg/kg Exposure1 (mg/kg Total Exposure2 Percent Acute RfD3
bwt/day) bwt/day) (mg/kg bwt/day)
----------------------------------------------------------------------------------------------------------------
Children (1 to 6 years old) 0.0081 0.072 0.080 19%
----------------------------------------------------------------------------------------------------------------
1Residential Exposure = Total of imidacloprid exposure from incidental ingestion of residues on lawns from hand-
to-mouth transfer plus ingestion of pesticide-treated grass plus ingestion of soil from treated gardens.
2Total Exposure = Chronic Food Exposure plus Residential Exposure.
3Percent Acute RfD = Acute RfD (0.42 mg/kg bwt/day)/Total Exposure (mg/kg bwt/day) x 100%.
----------------------------------------------------------------------------------------------------------------
Short-Term Aggregate Exposure and Risk (Includes the Pet Use of Imidacloprid)
-----------------------------------------------------------------------------------------------------------------
Chronic Food Residential
Population Subgroup Exposure (mg/kg Exposure1 (mg/kg Total Exposure2 Percent Acute RfD3
bwt/day) bwt/day) (mg/kg bwt/day)
----------------------------------------------------------------------------------------------------------------
Children (1 to 6 years old) 0.0081 0.058 0.066 16%
----------------------------------------------------------------------------------------------------------------
1Residential Exposure = Total of imidacloprid exposure from incidental ingestion of residues on pets from hand-
to-mouth transfer.
2Total Exposure = Chronic Food Exposure plus Residential Exposure.
3Percent Acute RfD = Acute RfD (0.42 mg/kg bwt/day)/Total Exposure (mg/kg bwt/day) x 100%.
The estimated maximum concentrations of imidacloprid in surface and
ground water (50.9 and 0.605 g/mL, respectively) are less than
EPA's level of concern for imidacloprid in drinking water (600 g/mL) as
a contribution to short-term exposure from imidacloprid home garden,
turf and pet uses. Therefore, taking into account the present uses and
uses proposed in this action, EPA concludes with reasonable certainty
that residues of imidacloprid in drinking water (when considered along
with other sources of short-term exposure for which EPA has reliable
data) would not result in unacceptable levels of short-term aggregate
human health risk estimates at this time.
EPA bases this determination on a comparison of estimated maximum
concentrations of imidacloprid in surface water to the back-calculated
``level of concern'' for imidacloprid in drinking water. The level of
concern in drinking water was determined after EPA has considered all
other non-occupational human exposures for which it has reliable data,
including all current uses and uses considered in this action. The
estimates of imidacloprid in surface and ground water are derived from
water quality models that use conservative assumptions (health-
protective) regarding the pesticide transport from the point of
application to surface and ground water. Because EPA considers the
aggregate risk resulting from multiple exposure pathways associated
with a pesticide's uses, levels of concern in drinking water may vary
as those uses change. If new
[[Page 49848]]
uses are added in the future, EPA will reassess the potential impacts
of imidacloprid in drinking water as a part of the a short-term
aggregate risk assessment process.
As noted above, potential short-term exposure from drinking water
is at a level well below EPA's level of concern. EPA concludes the
short-term aggregate risk to the highest exposed population subgroup
from home garden, turf, and pet uses of imidacloprid does not exceed
our level of concern.
3. Chronic risk. The chronic dietary (food only) risk assessment
utilized the following exposure assumptions: (i) tolerance level
residues for the proposed tolerances of these petitions and all other
commodities with published or pending, permanent or time-limited,
imidacloprid tolerances; and (ii) percent crop-treated information on
some of these crops. Using the exposure assumptions described above,
EPA has concluded that aggregate exposure to imidacloprid from food
will utilize 6.8% of the Chronic RfD for the U.S. population. The major
identifiable subgroup with the highest aggregate exposure is infants
(discussed below in section E). EPA generally has no concern for
exposures below 100% of the RfD because the RfD represents the level at
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. Despite the potential for
exposure to imidacloprid in drinking water, EPA does not expect the
aggregate exposure to exceed 100% of the RfD.
4. Aggregate cancer risk for U.S. population. Imidacloprid has been
classified as a Group E chemical, no evidence of carcinogenicity for
humans. Therefore, a cancer risk assessment is not required.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the U.S. population from aggregate exposure to imidacloprid
residues.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children--i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of imidacloprid, EPA 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. of this unit. 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
post-natal 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 pre-and post-natal 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 inter- and intra-species
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 Agency 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:
a. 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.
b. 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.
c. 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.
ii. Conclusion. The toxicology data base for imidacloprid is
complete with respect to core requirements; however, a developmental
neurotoxicity study (Guideline No. 83-6) is required. Exposure data is
estimated based on data that reasonably accounts for potential
exposures; however, a study to quantify dislodgeable residues on
toddler's hands from pets treated with imidacloprid is required.
2. Acute risk. Aggregate acute risks for the entire U.S. population
and for population subgroups, including infants and children, are
discussed in section D.1. of this unit.
3. Short- and intermediate-term risk. Aggregate short- and
intermediate-term risks for the entire U.S. population and for
population subgroups, including infants and children are discussed in
section D.2. of this unit.
4. Chronic risk. Using the exposure assumptions described above,
EPA has concluded that aggregate exposure to imidacloprid from food
will utilize 5.6% of the RfD for nursing infants, 19% of the RfD for
non-nursing infants, 14% of the RfD for children 1 to 6 years old, and
10% of the RfD for children 7 to 12 years old. EPA generally has no
concern for exposures below 100% of the RfD because the RfD represents
the level at or below which daily aggregate dietary exposure over a
lifetime will not pose appreciable risks to human health. Despite the
potential for exposure to imidacloprid in drinking water, EPA does not
expect the aggregate exposure to exceed 100% of the RfD.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to imidacloprid
residues.
III. Other Considerations
A. Metabolism in Plants and Animals
1. Nature of the residue in plants and livestock. Data concerning
the metabolism of imidacloprid in apples, potatoes, tomatoes, eggplant,
[[Page 49849]]
cottonseed, field corn, ruminants and poultry have previously been
submitted. The nature of imidacloprid residues in plants and animals is
adequately understood. The residue of concern is imidacloprid and its
metabolites containing the 6-chloropyridinyl moiety, all expressed as
parent, as specified in 40 CFR 180.472 (September 14, 1994, PP 4F4337
and September 23, 1997, PP 6F4765).
2. Confined accumulation in rotational crops. Data concerning the
metabolism of imidacloprid in rotational crops was previously
submitted. The nature of the residue in rotational crops is adequately
understood and is nearly identical to that identified in the primary
crops. The residue of concern in rotational crops is imidacloprid and
its metabolites containing the 6-chloropyridinyl moiety, all expressed
as parent (September 23, 1997, PP 6F4765).
B. Analytical Enforcement Methodology
Adequate enforcement methods are available for determination of the
regulated imidacloprid residue in plant (Bayer GC/MS Method 00200 and
Bayer HPLC-UV Confirmatory Method 00357) and animal (Bayer GC/MS Method
00191) commodities. These methods have successfully completed EPA
Tolerance Method Validation, and are awaiting publication in PAM II
(November 8, 1994 and April 13, 1995, PP 5F4415, June 17, 1996, PP
5F4480). In the interim, these methods are available from: Calvin
Furlow, PRRIB, IRSD (7502C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location and telephone number: Rm. 101FF, Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA, (703-305-5229).
Bayer Corporation has previously submitted adequate multiresidue
method (MRM) recovery data for imidacloprid and its olefin, hydroxy,
guanidine, and 6-chloronicotininc acid metabolites through FDA's
Protocols A through E. Imidacloprid and its metabolites were not
recoverable by these methods. These data have been forwarded to FDA and
we expect them to be published in PAM, Vol. I, Appendix I in a future
update. Additional MRM recovery data are not required (June 18, 1993,
PP 3F4169).
C. Magnitude of Residues
1. Crop field trials. The results of the previously submitted
wheat, barley, and sugar beet field trials support the proposed
tolerances for combined residues of imidacloprid and its regulable
metabolites as follows (March 6, 1998, PP 4F4337):
------------------------------------------------------------------------
Proposed Tolerance
Crop Commodity (ppm)
------------------------------------------------------------------------
Beets, Sugar tops 0.5
roots 0.05
molasses 0.3
------------------------------------------------------------------------
Barley grain 0.05
straw 0.5
hay 0.5
------------------------------------------------------------------------
Wheat grain 0.05
forage 7.0
straw 0.5
hay 0.5
------------------------------------------------------------------------
Residue data for aspirated grain fractions were not required for this
seed treatment use (September 14, 1994, PP 4F4337).
2. Field accumulation in rotational crops. The results of the
previously submitted rotational crop field trials support the proposed
tolerances for inadvertent or indirect combined residues of
imidacloprid and its regulable metabolites as follows (September 23,
1997, PP 6F4765):
------------------------------------------------------------------------
Crop Group or Crop Commodity Tolerance Level (ppm)
------------------------------------------------------------------------
Cereal Grains (Crop Group) grain 0.05
------------------------------------------------------------------------
Forage, Fodder and Straw of forage 2.0
Cereal Grains Crop Group straw 3.0
hay 6.0
stover 0.3
------------------------------------------------------------------------
Sweet Corn K+CWHR 0.05
------------------------------------------------------------------------
Safflower seed 0.05
meal 0.5
------------------------------------------------------------------------
Legume Vegetables (Crop seed 0.3
Group)
------------------------------------------------------------------------
Foliage of Legume Vegetables foliage 2.5
(Crop Group)
------------------------------------------------------------------------
Soybean meal 0.5
------------------------------------------------------------------------
K+CWHR = Kernel plus cob with husk removed.
[[Page 49850]]
3. Magnitude of the residue in processed food/feed--i. Wheat. The
results of a previously submitted wheat processing study showed that
residues of imidacloprid and its metabolites are not expected to
concentrate into the processed products of wheat. The study utilized a
5x exaggerated application rate (September 14, 1994 and May 16, 1995,
PP 4F4337).
ii. Sugar beets. The results of a previously submitted sugar beet
processing study (2.7x exaggerated application rate) showed that
residues of imidacloprid and its metabolites are not expected to
concentrate into dehydrated pulp. However, the results did show
residues are expected to concentrate into sugar beet molasses. A
tolerance of 0.3 ppm is adequate for residues of imidacloprid and its
metabolites in sugar beet molasses (September 14, 1994 and May 16,
1995, PP 4F4337).
iii. Barley. Processing data for barley were not required for this
seed treatment use (September 14, 1994, PP 4F4337).
iv. Field corn. The results of a previously submitted field corn
processing study showed that residues of imidacloprid and its
metabolites are not expected to concentrate into the processed products
of field corn. The study utilized exaggerated application rates of 2.5x
and 4x (February 19, 1998, PP 6F4765).
v. Safflower. A safflower processing study has not been submitted.
The petitioner has indicated that they intend to conduct a safflower
processing study. This deficiency is not resolved. A safflower
processing study for imidacloprid is required. EPA recommends in favor
of the proposed tolerances for imidacloprid and its metabolites in/on
safflower seed and meal provided the requirement for a safflower
processing study is made a condition of the registration of
imidacloprid on safflower. The proposed tolerances are based upon a
maximum residue level of <0.05 ppm="" (estimated="" to="" be="" approximately="" 0.03="" ppm)="" for="" total="" imidacloprid="" residues="" in="" safflower="" seed="" and="" a="" theoretical="" maximum="" concentration="" factor="" of="" 9.1x="" for="" safflower="" meal="" (september="" 23,="" 1997="" and="" february="" 19,="" 1998,="" pp="" 6f4765).="" vi.="" soybeans.="" a="" soybean="" processing="" study="" has="" not="" been="" submitted.="" the="" petitioner="" has="" proposed="" establishing="" a="" permanent="" tolerance="" for="" the="" combined="" residues="" of="" imidacloprid="" and="" its="" metabolites="" containing="" the="" 6-="" chloropyridinyl="" moiety="" in="" soybean="" meal="" at="" 0.5="" ppm="" in="" lieu="" of="" providing="" a="" soybean="" processing="" study.="" this="" request="" is="" based="" upon="" a="" maximum="" residue="" level="" of="" 0.2="" ppm="" for="" total="" imidacloprid="" residues="" in="" soybean="" seed="" and="" a="" theoretical="" maximum="" concentration="" factor="" of="" 2.2x="" for="" soybean="" meal.="" epa="" has="" considered="" this="" issue="" and="" has="" concluded="" that="" the="" requirement="" for="" a="" soybean="" processing="" study="" should="" be="" made="" a="" condition="" of="" the="" registration="" of="" imidacloprid="" on="" soybeans.="" thus,="" a="" soybean="" processing="" study="" is="" required.="" the="" proposed="" tolerances="" for="" imidacloprid="" and="" its="" metabolites="" for="" soybean="" seed="" and="" meal="" are="" adequate="" pending="" submission="" of="" the="" soybean="" processing="" study="" (february="" 19,="" 1998,="" pp="" 6f4765).="" 4.="" magnitude="" of="" secondary="" residues="" in="" meat,="" milk,="" poultry="" eggs--i.="" ruminants.="" a="" ruminant="" feeding="" study="" was="" previously="" submitted.="" epa="" has="" estimated="" the="" maximum="" imidacloprid="" dietary="" burden="" from="" proposed="" and="" established="" imidacloprid="" tolerances.="" the="" total="" dietary="" burden="" from="" our="" worst="" case="" diet="" for="" dairy="" cattle="" is="" approximately="" 20="" ppm.="" the="" total="" dietary="" burden="" from="" our="" worst="" case="" diet="" for="" beef="" cattle="" is="" approximately="" 12="" ppm.="" tolerances="" are="" established="" for="" the="" combined="" residues="" of="" imidacloprid="" and="" its="" metabolites="" containing="" the="" 6-="" chloropyridinyl="" moiety,="" expressed="" as="" imidacloprid,="" in="" ruminant="" fat,="" meat,="" and="" meat="" byproducts="" at="" 0.3="" ppm="" and="" in="" milk="" at="" 0.1="" ppm.="" epa="" concludes="" the="" established="" tolerances="" for="" imidacloprid="" and="" its="" metabolites="" in="" ruminant="" commodities="" will="" not="" be="" exceeded="" as="" a="" result="" of="" additional="" dietary="" burden="" from="" the="" tolerances="" proposed="" in="" these="" petitions="" (september="" 21,="" 1993,="" pp="" 3f4169="" and="" march="" 6,="" 1998,="" pp="" 4f4337).="" ii.="" poultry.="" a="" poultry="" feeding="" study="" was="" previously="" submitted.="" epa="" has="" estimated="" the="" maximum="" imidacloprid="" dietary="" burden="" for="" poultry="" from="" proposed="" and="" established="" imidacloprid="" tolerances.="" the="" total="" dietary="" burden="" from="" our="" worst="" case="" diet="" for="" poultry="" is="" approximately="" 2.2="" ppm.="" tolerances="" are="" established="" for="" the="" combined="" residues="" of="" imidacloprid="" and="" its="" metabolites="" containing="" the="" 6-chloropyridinyl="" moiety,="" expressed="" as="" imidacloprid,="" in="" poultry="" fat,="" meat="" and="" meat="" byproducts="" at="" 0.05="" ppm="" and="" in="" eggs="" at="" 0.02="" ppm.="" epa="" concludes="" the="" established="" tolerances="" for="" imidacloprid="" and="" its="" metabolites="" in="" poultry="" commodities="" will="" not="" be="" exceeded="" as="" a="" result="" of="" additional="" dietary="" burden="" from="" the="" tolerances="" proposed="" in="" these="" petitions="" (september="" 21,="" 1993,="" pp="" 3f4169="" and="" march="" 6,="" 1997,="" pp="" 4f4337).="" d.="" international="" residue="" limits="" there="" are="" no="" established="" codex,="" canadian,="" or="" mexican="" residue="" limits="" for="" imidacloprid="" in/on="" the="" crop="" groups="" cereal="" grains,="" legume="" vegetables="" and="" the="" foliage="" of="" legume="" vegetables;="" and="" the="" crops="" sweet="" corn,="" safflower,="" wheat,="" barley="" and="" sugar="" beets.="" thus,="" harmonization="" of="" the="" proposed="" tolerances="" with="" codex,="" canada,="" and="" mexico="" is="" not="" an="" issue="" for="" these="" petitions.="" iv.="" conclusion="" therefore,="" the="" tolerances="" are="" established="" for="" the="" combined="" residues="" of="" imidacloprid="" (1-[(6-chloro-3-pyridinyl)="" methyl]-n-nitro-2-="" imidazolidinimine)="" and="" its="" metabolites="" containing="" the="" 6-chloropyridinyl="" moiety,="" all="" expressed="" as="" (1-[(6-chloro-3-pyridinyl)="" methyl]-n-nitro-2-="" imidazolidinimine)="" in="" or="" on="" sugar="" beets="" -tops="" at="" 0.5,="" roots="" at="" 0.05,="" molasses="" at="" 0.3="" parts="" per="" million="" (ppm),="" barley="" -="" grain="" at="" 0.05,="" straw="" at="" 0.5,="" hay="" at="" 0.5="" ppm,="" wheat="" -="" grain="" at="" 0.05,="" forage="" at="" 7.0,="" straw="" at="" 0.5,="" hay="" at="" 0.5="" ppm="" (40="" cfr="" 180.472(a));="" and="" cereal="" grains="" crop="" group="" -="" grain="" at="" 0.05,="" forage="" at="" 2.0,="" straw="" at="" 3.0,="" hay="" at="" 6.0,="" stover="" at="" 0.3="" ppm,="" sweet="" corn="" (k+cwhr)="" at="" 0.05,="" safflower="" -="" seed="" at="" 0.05,="" meal="" at="" 0.5,="" legume="" vegetable="" crop="" group="" seed="" at="" 0.3,="" foliage="" at="" 2.5,="" soybean="" meal="" at="" 0.5="" ppm="" (inadvertent="" or="" indirect="" residues,="" 40="" cfr="" 180.472(d)).="" v.="" objections="" and="" hearing="" requests="" the="" new="" ffdca="" section="" 408(g)="" provides="" essentially="" the="" same="" process="" for="" persons="" to="" ``object''="" to="" a="" tolerance="" regulation="" issued="" by="" epa="" under="" new="" section="" 408(e)="" and="" (l)(6)="" as="" was="" provided="" in="" the="" old="" section="" 408="" and="" in="" section="" 409.="" however,="" the="" period="" for="" filing="" objections="" is="" 60="" days,="" rather="" than="" 30="" days.="" epa="" currently="" has="" procedural="" regulations="" which="" govern="" the="" submission="" of="" objections="" and="" hearing="" requests.="" these="" regulations="" will="" require="" some="" modification="" to="" reflect="" the="" new="" law.="" however,="" until="" those="" modifications="" can="" be="" made,="" epa="" will="" continue="" to="" use="" those="" procedural="" regulations="" with="" appropriate="" adjustments="" to="" reflect="" the="" new="" law.="" any="" person="" may,="" by="" november="" 17,="" 1998,="" file="" written="" objections="" to="" any="" aspect="" of="" this="" regulation="" and="" may="" also="" request="" a="" hearing="" on="" those="" objections.="" objections="" and="" hearing="" requests="" must="" be="" filed="" with="" the="" hearing="" clerk,="" at="" the="" address="" given="" above="" (40="" cfr="" 178.20).="" a="" copy="" of="" the="" objections="" and/or="" hearing="" requests="" filed="" with="" the="" hearing="" clerk="" should="" be="" submitted="" to="" the="" opp="" docket="" for="" this="" rulemaking.="" the="" objections="" submitted="" must="" specify="" the="" provisions="" of="" the="" regulation="" deemed="" objectionable="" and="" the="" grounds="" for="" the="" objections="" (40="" cfr="" 178.25).="" each="" objection="" must="" be="" accompanied="" by="" the="" fee="" prescribed="" by="" 40="" cfr="" 180.33.="" if="" a="" hearing="" is="" requested,="" [[page="" 49851]]="" the="" objections="" must="" include="" a="" statement="" of="" the="" factual="" issues="" on="" which="" a="" hearing="" is="" requested,="" the="" requestor's="" contentions="" on="" such="" issues,="" and="" a="" summary="" of="" any="" evidence="" relied="" upon="" by="" the="" requestor="" (40="" cfr="" 178.27).="" a="" request="" for="" a="" hearing="" will="" be="" granted="" if="" the="" administrator="" determines="" that="" the="" material="" submitted="" shows="" the="" following:="" there="" is="" genuine="" and="" substantial="" issue="" of="" fact;="" there="" is="" a="" reasonable="" possibility="" that="" available="" evidence="" identified="" by="" the="" requestor="" would,="" if="" established,="" resolve="" one="" or="" more="" of="" such="" issues="" in="" favor="" of="" the="" requestor,="" taking="" into="" account="" uncontested="" claims="" or="" facts="" to="" the="" contrary;="" and="" resolution="" of="" the="" factual="" issues="" in="" the="" manner="" sought="" by="" the="" requestor="" would="" be="" adequate="" to="" justify="" the="" action="" requested="" (40="" cfr="" 178.32).="" information="" submitted="" in="" connection="" with="" an="" objection="" or="" hearing="" request="" may="" be="" claimed="" confidential="" by="" marking="" any="" part="" or="" all="" of="" that="" information="" as="" confidential="" business="" information="" (cbi).="" information="" so="" marked="" will="" not="" be="" disclosed="" except="" in="" accordance="" with="" procedures="" set="" forth="" in="" 40="" cfr="" part="" 2.="" a="" copy="" of="" the="" information="" that="" does="" not="" contain="" cbi="" must="" be="" submitted="" for="" inclusion="" in="" the="" public="" record.="" information="" not="" marked="" confidential="" may="" be="" disclosed="" publicly="" by="" epa="" without="" prior="" notice.="" vi.="" public="" record="" and="" electronic="" submissions="" epa="" has="" established="" a="" record="" for="" this="" rulemaking="" under="" docket="" control="" number="" opp-300717="" (including="" any="" comments="" and="" data="" submitted="" electronically).="" a="" public="" version="" of="" this="" record,="" including="" printed,="" paper="" versions="" of="" electronic="" comments,="" which="" does="" not="" include="" any="" information="" claimed="" as="" cbi,="" is="" available="" for="" inspection="" from="" 8:30="" a.m.="" to="" 4="" p.m.,="" monday="" through="" friday,="" excluding="" legal="" holidays.="" the="" public="" record="" is="" located="" in="" rm.="" 119="" of="" the="" public="" information="" and="" records="" integrity="" branch,="" information="" resources="" and="" services="" division="" (7502c),="" office="" of="" pesticide="" programs,="" environmental="" protection="" agency,="" crystal="" mall="" #2,="" 1921="" jefferson="" davis="" hwy.,="" arlington,="" va.="" electronic="" comments="" may="" be="" sent="" directly="" to="" epa="" at:="">opp-docket@epamail.epa.gov.
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This final rule establishes tolerances for imidacloprid under FFDCA
section 408(d) in response to a petition submitted to the Agency. The
Office of Management and Budget (OMB) has exempted these types of
actions from review under Executive Order 12866, entitled ``Regulatory
Planning and Review'' (58 FR 51735, October 4, 1993). This final rule
does not contain any information collections subject to OMB approval
under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or
impose any enforceable duty or contain any unfunded mandate as
described under Title II of the Unfunded Mandates Reform Act of 1995
(UMRA) (Pub. L. 104-4). Nor does it require any special considerations
as required by Executive Order 12898, entitled ``Federal Actions to
Address Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require OMB review in
accordance with Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997). In addition, since tolerances and exemptions that are
established on the basis of a petition under FFDCA section 408(d), such
as the tolerances for imidacloprid in this final rule, do not require
the issuance of a proposed rule, the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply.
Nevertheless, the Agency has previously assessed whether establishing
tolerances, exemptions from tolerances, raising tolerance levels, or
expanding exemptions might adversely impact small entities and
concluded, as a generic matter, that there is no adverse economic
impact. The factual basis for the Agency's generic certification for
tolerance actions published on May 4, 1981 (46 FR 24950) and was
provided to the Chief Counsel for Advocacy of the Small Business
Administration.
B. Executive Order 12875
Under Executive Order 12875, entitled ``Enhancing Intergovernmental
Partnerships'' (58 FR 58093, October 28, 1993), EPA may not issue a
regulation that is not required by statute and that creates a mandate
upon a State, local or Tribal government, unless the Federal government
provides the funds necessary to pay the direct compliance costs
incurred by those governments. If the mandate is unfunded, EPA must
provide to OMB a description of the extent of EPA's prior consultation
with representatives of affected State, local and Tribal governments,
the nature of their concerns, copies of any written communications from
the governments, and a statement supporting the need to issue the
regulation. In addition, Executive Order 12875 requires EPA to develop
an effective process permitting elected officials and other
representatives of State, local and Tribal governments ``to provide
meaningful and timely input in the development of regulatory proposals
containing significant unfunded mandates.''
Today's rule does not create an unfunded Federal mandate on State,
local or Tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled ``Consultation and
Coordination with Indian Tribal Governments'' (63 FR 27655, May 19,
1998), EPA may not issue a regulation that is not required by statute,
that significantly or uniquely affects the communities of Indian tribal
governments, and that imposes substantial direct compliance costs on
those communities, unless the Federal government provides the funds
necessary to pay the direct compliance costs incurred by the Tribal
governments. If the mandate is unfunded, EPA must provide OMB, in a
separately identified section of the preamble to the rule, a
description of the extent of EPA's prior consultation with
representatives of affected Tribal governments, a summary of the nature
of their concerns, and a statement supporting the need to issue the
regulation. In addition, Executive Order 13084 requires EPA to develop
an effective process permitting elected and other representatives of
Indian tribal governments ``to provide meaningful and timely input in
the development of regulatory policies on matters that
[[Page 49852]]
significantly or uniquely affect their communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian Tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. This rule is not a
``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: September 9, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
Sec. 180.472 [Amended]
2. Section 180.472 is amended by adding the commoditiy wheat (hay)
to the table in paragraph (a) and revising the following entries to
paragraphs (a) and (d) to read as follows:
(a) * * *
------------------------------------------------------------------------
Expiration/
Commodity Parts per Revocation
million date
------------------------------------------------------------------------
* * * * *
Barley (grain)................................ 0.05 None
Barley (hay).................................. 0.5 None
Barley (straw)................................ 0.5 None
* * * * *
Beets, sugar (tops)........................... 0.5 None
Beets, sugar (roots).......................... 0.05 None
Beets, sugar, molasses........................ 0.3 None
* * * * *
Wheat (forage)................................ 7.0 None
Wheat (grain)................................. 0.05 None
Wheat (hay)................................... 0.5 None
Wheat (straw)................................. 0.5 None
------------------------------------------------------------------------
* * * * *
(d) * * *
------------------------------------------------------------------------
Expiration/
Commodity Parts per Revocation
million date
------------------------------------------------------------------------
Cereal grains crop group (grain).............. 0.05 None
Foliage of legume vegetables crop group
(foliage).................................... 2.5 None
Forage, fodder, and straw of cereal grains
crop group (forage).......................... 2.0 None
Forage, fodder, and straw of cereal grains
crop group (hay)............................. 6.0 None
Forage, fodder, and straw of cereal grains
crop group (stover).......................... 0.3 None
Forage, fodder, and straw of cereal grains
crop group (straw)........................... 3.0 None
Legume vegetables crop group (seed)........... 0.3 None
Safflower (meal).............................. 0.5 None
Safflower (seed).............................. 0.05 None
Soybean (meal)................................ 0.5 None
Sweet corn (kernel plus cob with husk removed) 0.05 None
* * * * *
------------------------------------------------------------------------
FR Doc. 98-25085 Filed 9-17-98; 8:45 am
BILLING CODE 6560-50-F
