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Adverse Effects
Abstracts
ACTIVITY:
Insecticide
(oxadiazine)
CAS Name:
methyl (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-
(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate
EPA,
as of June 9, 2004, Indoxacarb:
(S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]
amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate
EPA, as of June 9, 2004,R-enantimomer:
(R)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]
carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate
Structure
of Indoxacarb:
|
Published
Date |
Docket
Identification Number |
Details |
July 11, 2007 |
EPA-HQ-OPP-2005-0149 |
E.I. du Pont de
Nemours and Company and IR4.
Pesticide
tolerance. FINAL RULE.
Tolerances are established for the combined
residues of the insecticide indoxacarb and its R-enantiomer,
(R)- methyl 7-chloro-2,5-dihydro-2[[(methoxycarbonyl)[4(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4][oxadiazine-4a(3H)-carboxylate,
in or on the following raw agricultural commodities:
DOCUMENTS AVAILABLE WITH
THIS FINAL RULE: |
NOF: Indoxacarb in/on cucurbit vegetable
group 9, stone fruit, and cranberry
Docket: EPA-HQ-OPP-2005-0149-0003 |
Indoxacarb. Health Effects Division (HED)
Risk Assessment for Grapes; Vegetable, Brassica, Leafy,
Group 5; Turnip Greens; Vegetable, Leafy, Except Brassica
(Group 4); Pome Fruits (Group 11, except pear); Tuberous
and Corm Vegetables (Subgroup 1C); Cucurbit Vegetables
(Group 9); Stone Fruits (Group 12); Cranberry; Mint; Okra;
Southern Pea; and Fire Ant Bait.
Docket: EPA-HQ-OPP-2005-0149-0005 |
Indoxacarb: Acute and Chronic Dietary
Exposure and Risk Assessments for the Proposed Section
3 Registrations and Petitions for Tolerances on Grapes;
Vegetable, Brassica, Leafy, Group 5; ...; Pome Fruits
(Group 11, except pear); Tuberous and Corm Vegetables
(Subgroup 1C); Cucurbit Vegetables (Group 9); Stone Fruits
(Group 12); Cranberry; Mint; Okra; and Southern Pea.
Docket: EPA-HQ-OPP-2005-0149-0006 |
Indoxacarb. Petitions for Tolerances
on Vegetable, Leafy, Except Brassica (Group 4), Pome Fruits
(Group 11, except pear), Tuberous
Docket: EPA-HQ-OPP-2005-0149-0007 |
Commodity |
Parts
per million |
Apple, wet pomace |
3.0 |
Alfalfa, forage |
10 |
Alfalfa, hay |
50 |
Cattle, fat |
1.5 |
Cattle, meat |
0.05 |
Cattle, meat byproducts |
0.03 |
Corn, sweet, forage
|
10 |
Corn, sweet, kernel plus cob with husk
removed |
0.02 |
Corn, sweet, stover |
15 |
Cotton, gin byproducts |
15 |
Cotton, undelinted seed |
2.0 |
Cranberry |
0.90 |
Fruit, pome, except pear, group
11
This group includes
10 commodities.
apple • apple, dried pomace • apple, juice
• apple, wet pomace • crabapple •
fruit, pome • loquat • mayhaw •
pear • pear, oriental • quince
|
1.0 |
Fruit, stone, group
12
This group includes
14 commodities.
apricot • cherry, sweet • cherry, tart
• fruit, stone • fruit, stone, except
plum, prune, dried • nectarine • peach
• plum • plum, chickasaw • plum,
damson • plum, japanese • plum, prune
• plum, prune, dried • plum, prune, fresh
|
0.90 |
Goat, fat |
1.5 |
Goat, meat |
0.05 |
Goat, meat byproducts |
0.03 |
Grape |
2.0 |
Grape, raisin |
5.0 |
Hog, fat |
1.5 |
Hog, meat |
0.05 |
Hog, meat byproducts |
0.03 |
Horse, fat |
1.5 |
Horse, meat |
0.05 |
Horse, meat byproducts |
0.03 |
Milk |
0.15 |
Milk, fat |
4.0 |
Okra |
0.50 |
Pea, southern, seed |
0.10 |
Peanut |
0.01 |
Peanut, hay |
40 |
Pear |
0.20 |
Pear, oriental |
0.20 |
Peppermint, tops |
11 |
Sheep, fat |
1.5 |
Sheep, meat |
0.05 |
Sheep, meat byproducts |
0.03 |
Soybean, aspirated grain fractions |
45 |
Soybean, hulls |
4.0 |
Soybean, seed |
0.80 |
Spearmint, tops |
11 |
Turnip, greens |
12 |
Vegetable, Brassica, leafy, group
5
This group includes
16 commodities.
broccoli • broccoli raab
• broccoli, chinese • brussels sprouts
• cabbage • cabbage, chinese, bok choy
• cabbage, chinese, mustard • cabbage,
chinese, napa • cauliflower • collards
• kale • kohlrabi • mustard greens
• mustard spinach • rape greens •
vegetable, brassica, leafy, group
|
12 |
Vegetable, cucurbit, group
9
This group includes
19 commodities.
balsam apple • balsam pear • cantaloupe
• chayote, fruit • cucumber • cucumber,
chinese • cucurbits • gherkin, west indian
• gourd, edible • melon • melon,
citron • muskmelon • pumpkin • squash
• squash, summer • squash, winter •
vegetable, cucurbit, group • watermelon •
waxgourd, chinese
|
0.60 |
Vegetable, fruiting, group
8
This group includes
17 commodities.
chili, postharvest • eggplant • groundcherry
• pepino • pepper • pepper, bell
• pepper, nonbell • pepper, nonbell, sweet
• tomatillo • tomato • tomato, concentrated
products • tomato, dried pomace • tomato,
paste • tomato, puree • tomato, wet pomace
• vegetable, fruiting • vegetable, fruiting,
group
|
0.50 |
Vegetable, leafy, except Brassica,
group 4
This group includes
37 commodities.
amaranth, leafy • arugula • cardoon •
celery • celery, chinese • celtuce •
chervil • chervil, fresh leaves • chrysanthemum,
edible leaved • chrysanthemum, garland •
corn salad • cress, garden • cress, upland
• dandelion, leaves • dock • endive
• fennel, florence • fennel, florence,
fresh leaves and stalk • kale, sea • lettuce,
head • lettuce, leaf • orach • orach,
leaves • parsley • parsley, leaves •
purslane, garden • purslane, winter •
radicchio • rhubarb • spinach •
spinach, chinese • spinach, new zealand •
spinach, vine • swiss chard • tampala
• vegetable, leafy • vegetable, leafy,
except brassica, group
|
14 |
Vegetable, tuberous and corm, subgroup
1-C
This subgroup includes
22 commodities.
arracacha • arrowroot • artichoke, chinese
• artichoke, jerusalem • canna, edible
• cassava • chayote root • chufa
• dasheen • ginger • leren •
potato • potato culls • potato granules
flakes • potato peel, wet • potato processed
potato waste • potato, specialty • sweet
potato • tanier • turmeric • yam
bean • yam, true
|
0.01 |
|
April 12, 2006 |
EPA-HQ-OPP-2005-0149 |
IR-4.
Pesticide
petition: PP 5E6991 for Indoxacarb and its R-enantiomer
-- vegetable, cucurbit, group 9
at 0.5 ppm
This group includes 19 commodities.
balsam apple • balsam pear • cantaloupe •
chayote, fruit • cucumber • cucumber, chinese
• cucurbits • gherkin, west indian • gourd,
edible • melon • melon, citron • muskmelon
• pumpkin • squash • squash, summer •
squash, winter • vegetable, cucurbit, group •
watermelon • waxgourd, chinese
-- fruit, stone, group
12 at 1.0 ppm
This group includes 14 commodities.
apricot • cherry, sweet • cherry, tart •
fruit, stone • fruit, stone, except plum, prune, dried
• nectarine • peach • plum • plum,
chickasaw • plum, damson • plum, japanese •
plum, prune • plum, prune, dried • plum, prune,
fresh
-- cranberry at 1.0 ppm. |
August
31, 2005 |
OPP-2005-0223 |
Pesticide
Emergency Exemptions:
•
Massachusetts. EPA authorized the use
of indoxacarb on cranberry to
control cranberry weevil; May 12, 2005 to June 30, 2005. Contact:
(Stacey Groce) |
June
30, 2005 |
OPP-2005-0149 |
IR-4
& DuPont.
Pesticide Petition
for Indoxacarb and its R-enantiomer; in or on the following
raw agricultural commodities:
Pesticide
Petition |
Commodity |
PPM |
PP
5E6911 |
leafy
greens, except spinach, subgroup
4A
This
subgroup includes 24 commodities.
amaranth, grain • arugula • chervil •
chrysanthemum, edible leaved • chrysanthemum,
garland • corn salad • cress, garden •
cress, upland • dandelion • dock •
endive • lettuce • lettuce, head •
lettuce, leaf • orach • parsley •
purslane, garden • purslane, winter • radicchio
• spinach • spinach, chinese • spinach,
new zealand • spinach, vine • tampala |
10 |
PP
5E6911 |
spinach
|
3 |
PP
5E6911 |
leafy
petioles subgroup
4B
This
subgroup includes 8 commodities:
amaranth, leafy • cardoon • celery •
celery, chinese • celtuce • fennel, florence
• rhubarb • swiss chard |
1.5
|
PP
5E6911 |
fruit, pome, except pear, group
11
This
group includes 14 commodities:
pricot • cherry, sweet •
cherry, tart • fruit, stone • fruit, stone,
except plum, prune, dried • nectarine •
peach • plum • plum, chickasaw • plum,
damson • plum, japanese • plum, prune •
plum, prune, dried • plum, prune, fresh |
1.0 |
PP
5E6911 |
vegetable,
tuberous and corm, subgroup
1C
This
subgroup includes 22 commodities:
arracacha • arrowroot • artichoke, chinese
• artichoke, jerusalem • canna, edible •
cassava • chayote root • chufa • dasheen
• ginger • leren • potato •
potato culls • potato granules flakes •
potato peel, wet • potato processed potato waste
• potato, specialty • sweet potato •
tanier • turmeric • yam bean • yam,
true |
0.01 |
PP
5E6911 |
okra |
0.5
|
PP
5E6929 |
pea,
southern |
0.1 |
PP
5E6929 |
peppermint,
tops |
10 |
PP
5E6929 |
spearmint,
tops |
10 |
Residue
Chemistry. The
active ingredient in the end-use formulation,
DuPont\TM\ Avaunt[reg] insecticide, is a 75:25 mixture of
two isomers, indoxacarb (DPX-KN128) and IN-KN127. Only one
of the isomers, indoxacarb (DPX-KN128), has insecticidal activity.
Since the insecticidal efficacy is based on the concentration
of indoxacarb (DPX-KN128), the application rates have been
normalized on an indoxacarb (DPX-KN128) basis. The
proposed tolerance expression includes both indoxacarb (DPX-KN128)
and IN-KN127, and the residue method does not distinguish
between the enantiomers. Therefore, residues are reported
as the sum of indoxacarb
(DPX-KN128) combined with IN-KN127. Residues of indoxacarb
(DPX-KN128) combined with IN-KN127 will be referred to as
KN128/KN127.
Acute
neurotoxicity study.
•
In
an acute neurotoxicity study, indoxacarb exhibited decreased
forelimb grip strength, decreased foot splay, and some evidence
of slightly reduced motor activity, but only at the highest
doses tested. The no observed adverse
effect level (NOAEL) was 100
milligrams/kilogram (mg/kg) for males, and
12.5 mg/kg for females,
based on body weight effects in females 50 mg/kg.
Reproductive
and developmental toxicity.
• In
a 2-generation rat reproduction study, the parental NOAEL
was 1.5 mg/kg/day. The parental NOAEL was based on observations
of reduced weight gain and food
consumption for the higher concentration groups of the F 0
generation and potential treatment-related
changes in spleen weights for the higher groups of
the F 1 generation.
•
The NOAEL for fertility and reproduction was 6.4 mg/kg/day.
The offspring NOAEL was 1.5 mg/kg/day, and was based on the
reduced mean pup weights noted
for the F 1 litters of the higher concentration groups.
•
Developmental studies conducted in rats and rabbits demonstrated
that the rat was more susceptible than
the rabbit to the maternal and fetal effects of DPX-
MP062.
•
The NOAEL for maternal and fetal effects
in rats was 2 mg/kg/day based on body
weight effects and decreased food consumption at 4
mg/kg/day.
•
The
NOAEL for developmental effects in fetuses was >4 mg/kg/day.
In rabbits, the maternal and fetal NOAELS were 500 mg/kg/day
based on body weight effects,
decreased food consumption in dams and decreased
weight and delayed ossification in fetuses at 1,000
mg/kg/day.
Chronic
toxicity.
•
The
chronic
NOAEL
in male rats was 5 mg/kg/day based on body
weight and nutritional effects. In
females, the NOAEL of 2.1 mg/kg/day was based
on body weight and nutritional changes, as well as biologically
significant hematologic changes at 3.6 mg/kg/day and above.
Hemolytic effects were present only through the 6-month evaluation
and only in females.
•
In
mice,
the chronic NOAEL of 2.6 mg/kg/day for males was based on
deceased body weight and weight gain effects and food efficiency
at 13.8 mg/kg/day and above. The NOAEL for females was 4.0
mg/kg/day based on body weight nutritional effects, neurotoxicity,
and clinical signs at 20 mg/kg/day. In dogs, the chronic NOAEL
was about 2.3 and 2.4 mg/kg/day in males and females, respectively
based on hemolytic effects similar to those seen in the subchronic
dog study.
Subchronic
toxicity.
•
Mice
were less sensitive to indoxacarb than the rats or dogs.
NOAELs (23 mg/kg/day, males, 16 mg/kg/day,
females) were based on mortality
(males only); increased reticulocytes and
Heinz bodies and decreased body weight, weight gain, food
consumption, food efficiency; and increased clinical signs
(leaning to one side and/or with abnormal gait or mobility)
(females only).
In a 28-day repeated dose dermal study, the NOAEL was 50 mg/kg/day
based on decreased body weights, body weight
gains, food consumption, and food efficiency in
females, and changes in hematology parameters,
the spleen and clinical signs of toxicity in both sexes in
rats. |
Feb
23, 2005 |
OPP-2005-0037 |
Pesticide
Emergency Exemptions.
• Georgia Department of Agriculture
Specific: EPA authorized the use of indoxacarb on collards
to control diamondback moth; November 4, 2004 to November 3,
2005. |
Nov
10, 2004 |
OPP-2004-0232 |
One
Pesticide Emergency Exemption.
• Massachusetts
- Specific: EPA authorized the use of indoxacarb
on cranberries to control cranberry
weevil; April 6, 2004 to August 1, 2004. Contact: (Barbara
Madden) |
Oct
27, 2004 |
OPP-2004-0338 |
Cancellation
of Pesticides for Non-payment of Year 2004 Registration Maintenance
Fees.
Table
1.--Section 24(c) Registrations Canceled for Non-Payment
of
Maintenance Fee |
Name
of Pesticide |
Product
Name |
Registrant |
SLN
No. |
Indoxycarb |
Avaunt
Insecticide |
E.
I. du Pont de Nemours and Co., Inc. |
074033
PR-01-0001 |
|
June
9, 2004 |
OPP-2004-0169 |
Tolerances
for Residues; Technical Correction. FINAL RULE.
EPA, in
making amendments to 40 CFR Part 180, has identified
typographical errors in the chemical name of indoxacarb throughout
this
section. This document is being issued to correct these typographical
errors.
(1) Tolerances are established
for the combined residues of the
insecticide indoxacarb, (S)-methyl
7-chloro-2,5-dihydro-2-
[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]
amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate,
and
its R-enantimomer, (R)-methyl
7-chloro-2,5-dihydro-2-
[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]
carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate,
in or on
the following raw agricultural commodities:
* * * * *
(2) Time-limited tolerances are
established for combined residues
of indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)
[4-(trifluoromethoxy) phenyl]amino]carbonyl]indeno[1,2-
e][1,3,4]oxadiazine-4a(3H)-carboxylate, and its R-enantiomer,
(R)-
methyl 7-chloro- 2,5-dihydro-2- [[(methoxycarbonyl)[4-
(trifluoromethoxy) phenyl]amino]carbonyl]indeno[1,2-e]
[1,3,4]oxadiazine-4a(3H)- carboxylate, in connection with
use of the
pesticide under FIFRA section 5 experimental use permit granted
by EPA.
The tolerances are specified in the following table, and will
expire
and are revoked on the dates specified.
* * * * *
(b) Time-limited tolerances are
established for the residues of
indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-
(trifluoromethoxy)phenyl]amino]carbonyl]indeno [1,2-e][1,3,4]oxadiazine-
4a(3H)-carboxylate, and its R-enantiomer,
(R)-methyl 7-chloro-2,5-
dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]
amino]
carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate,
in connection with use of the pesticide under section 18 emergency
exemptions granted by EPA. The tolerances are specified in
the following table, and will expire and are revoked on the
dates specified. |
May
24, 2004 |
OPP-2004-0136 |
Extension
of Tolerances for Emergency Exemptions. FINAL RULE.
EPA
has authorized under FIFRA section 18 the use of indoxacarb
on cranberry for control of weevils in
Massachusetts. This regulation extends a time-limited
tolerance for combined residues of the
insecticide indoxacarb and its R-enantiomer
in or on cranberry at 0.5 ppm for an additional
3-year period. This tolerance will expire
and is revoked on December 31, 2007. A time-limited tolerance
was originally published in the Federal Register of September
18, 2002. |
May
5, 2004 |
OPP-2004-0064 |
DUPONT;
IR-4.
Pesticide petition.
Proposal
to amend 40
CFR 180.564(a) by revoking Brassica, head and stem, subgroup
at 5.0
ppm, and establishing tolerances for residues of the insecticide,
indoxacarb and its R-enantiomer in or
on the raw agricultural commodities (RACs) vegetable, Brassica,
leafy, group 5 at 12 ppm, and turnip at 12 ppm.
Brassica,
leafy, group 5
includes |
broccoli
broccoli raab
broccoli, chinese
brussels sprouts
cabbage
cabbage, chinese, bok choy
cabbage, chinese, mustard
cabbage, chinese, napa
|
cauliflower
collards
kale
kohlrabi
mustard greens
mustard spinach
rape greens
|
-- An
assessment of the toxic effects caused by indoxacarb is discussed
in Unit III.A. and Unit III.B. of the Federal
Register dated July 2, 2003.
-- EPA's consideration of a common mechanism
of toxicity is not
necessary at this time because there is no indication
that toxic
effects of indoxacarb would be cumulative with those of any
other
chemical compounds. Oxadiazine chemistry
is new, and indoxacarb has a novel mode of action compared
to currently registered active ingredients. |
March
17, 2004 |
OPP-2004-0034 |
DuPont.
Indoxacarb and its R-enantiomer;
75:25 mixture (DPX MP062). Pesticide
tolerance petition. The
proposed tolerance expression includes both indoxacarb (DPX-KN128)
and IN-KN127 in
or on the raw agricultural commodity as follows:
cherry, sweet, 1 ppm and cherry, tart, 1 ppm.
•
Acute Oral Toxicity
LD50: 1,730 milligrams/kilogram (mg/kg) (male
rat)
LD50: 268 mg/kg (female
rat)
•
Acute
neurotoxicity study
- NOAEL)
was 100 mg/kg for males and 12.5
mg/kg for females based on body
weight effects in females
•
In a 2-generation rat reproduction study,
the parental NOAEL was 1.5 mg/kg/ day.
The parental NOAEL was based on observations of reduced
weight gain and food consumption for the higher concentration
groups of the F0 generation and potential treatment-related
changes in spleen weights or
the higher groups of the F1 generation... The
NOAEL for
fertility and reproduction was 6.4 mg/kg/day. The off spring
NOAEL was 1.5 mg/kg/day, and was based on the reduced mean
pup weights noted for the F1 litters of the higher concentration
groups.
•
Subchronic
toxicity.
In a 90-day feeding study in rats,
the NOAEL was 3.1 and 2.1 mg/kg/day for males and females,
respectively. In
male rats, the NOAEL was based on decreased body weight
and nutritional parameters, mild hemolytic anemia and decreased
total protein and globulin concentration. In
female rats, the NOAEL was based
on decreased body weight and food efficiency. The subchronic
NOAEL in dogs (5.0 mg/kg/day, modifying factor (M/F) was based
on hemolytic anemia.
•
Chronic toxicity. The
chronic NOAEL in male rats was
5 mg/ kg/day based on body weight and nutritional effects.
In females, the NOAEL of 2.1
mg/kg/day was based on body weight and nutritional changes,
as well as biologically significant hematologic changes at
3.6 mg/kg/day and above. Hemolytic
effects were present only through the 6- month evaluation
and only in females.
•
Dietary exposure.
The chronic RfD of 0.02 mg/kg bw/day is based on a NOAEL of
2.0 mg/kg bwt/day from the subchronic rat feeding study, the
subchronic rat neurotoxicity study, and the chronic/carcinogenicity
study, using an uncertainty factor of 100. The
acute RfD for the general population
is 0.12 mg/kg/day, based on the NOAEL of 12.5 mg/kg
in the acute neurotoxicity study and an uncertainty factor
of 100. The acute RfD for females
13-50 years of age is 0.02 mg/kg/day,
based on the NOAEL of 2 mg/kg/day observed in the developmental
rat toxicity study and using an uncertainty factor of 100. |
Nov
26, 2003 |
OPP-2003-0358 |
2
Pesticide Emergency Exemptions.
-- Georgia
Department of Agriculture. Specific. EPA authorized the use
of indoxacarb on collards to control
diamondback moth; April 20, 2003 to April 20, 2004.
-- Massachusetts Department of
Food and Agriculture. EPA authorized the use of indoxacarb
on cranberries to control
weevils; May 9, 2003 to September 30, 2003. |
July
18, 2003 |
OPP-2003-0197 |
DuPont.
Issuance
of Experimental Use Permit: 352-EUP-167
to E. I. Dupont de Nemours and Company,
P.O. Box 30, Newark, DE 19714. This EUP allows the use of 450
pounds of the insecticide Dupont Avaunt, containing 135
pounds of the active ingredient indoxacarb on 300 acres
of peaches to evaluate the control of the Oriental fruit
moth and plum curculio. The program is
authorized only in the States of Georgia, Michigan, New Jersey,
Pennsylvania, South Carolina, and West Virginia. The
EUP is effective from May 2, 2003 to May 2, 2005. |
July
2, 2003 |
OPP-2003-0212 |
DuPont.
Pesticide petition for
tolerances: grape, 2 ppm and
raisin, 6 ppm; to establish a tolerance for
combined residues of Indoxacarb and its and its R-enantiomer
in a 75:25 mixture (DPX MP062), in or
on the raw agricultural commodity: grape, 2 ppm and raisin,
6 ppm. The active ingredient in the end-use
formulation, Avaunt[Ograve], is a 75:25
mixture of two isomers, indoxacarb (DPX-KN128) and IN-KN127.
Only one of the isomers, indoxacarb (DPX-KN128), has insecticidal
activity.
-- In an acute neurotoxicity study, indoxacarb exhibited decreased
forelimb grip strength, decreased foot splay, and some evidence
of slightly reduced motor activity, but only at the highest
doses tested. The no adverse effects level (NOAEL) was 100
mg/kg for males and 12.5 mg/kg for females
based on body weight effects in females >50 mg/kg.
-- In a 2- generation rat reproduction
study, the parental NOAEL was 1.5 mg/kg/ day. The parental NOAEL
was based on observations of reduced weight gain and food consumption
for the higher concentration groups of the F0 generation, and
potential treatment-related changes in spleen weights for the
higher groups of the F1 generation.
-- The NOAEL for developmental effects in fetuses was >4 mg/kg/day.
In rabbits, the maternal and fetal NOAELS were 500 mg/kg/day
based on body weight effects, decreased food consumption in
dams and decreased weight and delayed
ossification in fetuses at 1,000 mg/kg/day.
-- Subchronic toxicity. Subchronic (90-day) feeding studies
were conducted with rats, mice, and dogs. In a 90-day feeding
study in rats, the NOAEL was 3.1 and 2.1 mg/kg/day for males
and females, respectively. In male rats, the NOAEL was based
on decreased body weight and nutritional
parameters, mild hemolytic anemia and
decreased total protein and globulin concentration. In
female rats, the NOAEL was based on decreased
body weight and food efficiency.
-- In a subchronic neurotoxicity study in rats, there was no
evidence of neurotoxicity at 11.9 and 6.09 mg/kg/day, the highest
dose tested for males and females,
respectively.
-- Chronic toxicity... The chronic NOAEL in male rats was 5
mg/ kg/day based on body weight and nutritional effects. In
females, the NOAEL of 2.1
mg/kg/day was based on body weight and nutritional changes,
as well as biologically significant hematologic
changes at 3.6 mg/kg/day and above. Hemolytic effects
were present only through the 6-month evaluation and only in
females. |
May
21, 2003 |
OPP-2003-0151 |
Pesticide
Tolerances for Emergency Exemptions. FINAL RULE.
This regulation establishes a time-limited tolerance for combined
residues of indoxacarb and its R-enantimomer in or on collards
at 3 ppm only in the State of Georgia. The
tolerance will expire and is revoked on June 30, 2006.
Refer to the July
18, 2002, Federal Register for detailed toxicological
information on indoxacarb. |
May
14, 2003 |
OPP-2003-0173 |
DuPont.
Time-Limited Pesticide
Tolerance for residues of Indoxacarb
and its R-enantiomer of 10 ppm in
or on Peaches in GA, MI, NJ, PA, SC, and WV. FINAL
RULE. This tolerance will expire and is revoked
on May 15, 2006. See below for adverse effects from animal
studies. |
Apr
16, 2003 |
OPP-2003-0125 |
Proposed
temporary 3-year tolerance for combined residues of the insecticide
Indoxacarb, in or on peaches at 10.0 ppm. This action
is in response to university extension
specialists, DuPont, and EPA's combined efforts to
generate the information necessary for registration of the
reduced risk pesticide, Indoxacarb, on peaches for control
of oriental fruit moth and plum cuculio. This proposed temporary
tolerance supports a non-crop destruct experimental use permit
(EUP) under section 5 of FIFRA authorizing use of Indoxacarb
on peaches in Georgia, Michigan, New Jersey, Pennsylvania,
South Carolina, and West Virginia.
---- 90-Day oral toxicity rodents.
DPX-MP062 NOAEL = M 3.1 mg/kg/day
F 2.1 mg/kg/day LOAEL = M 6.0 mg/kg/day, F 3.8 mg/kg/day based
on decreased body weight, body weight
gain, food consumption and food efficiency.
---- 90-Day oral toxicity in nonrodents.
DPX-JW062 NOAEL = 5.0 mg/kg/day
LOAEL = 19 mg/kg/day based on hemolytic anemia, as indicated
by decrease in HGB, RBCs; increases
in platelets, increased reticulocytes; and secondary
histopathologic findings indicative of blood
breakdown (pigment in Kupffer cells, renal tubular epithelium,
and spleen and bone marrow macrophages);
increase in splenic EMH; and RBC hyperplasia in bone marrow
in dogs.
---- Prenatal developmental in rodents.
DPX-MP062 Maternal NOAEL
= 2.0 mg/kg/day LOAEL = 4.0 mg/kg/day based on decreased mean
body weights, body weight gains, food consumption. Developmental
NOAEL = 2.0 mg/kg/day LOAEL = 4.0 mg/kg/day based on decreased
fetal weights. DPX-JW062 Maternal NOAEL = 10 mg/kg/day LOAEL
= 100 mg/kg/day based on mortality, clinical signs, and decreased
mean body weights, body weight gains, and food consumption.
Developmental NOAEL = 10 mg/kg/day LOAEL = 100 mg/kg/day based
on decreased numbers of live fetuses/litter.
DPX-JW062 Maternal
NOAEL = 1.1 mg/kg/day LOAEL = 2.2 mg/kg/day based on decreased
mean body weights, body weight gains, food consumption,
and food efficiency. Developmental NOAEL = 1.1 kg/day LOAEL
= 2.2 mg/kg/day based on decreased fetal
body weights.
---- Prenatal developmental in nonrodents.
DPX-JW062 - rabbits Maternal
NOAEL = 500 mg/kg/day LOAEL = 1,000 mg/kg/day based on slight
decreases in maternal body weight gain and food consumption.
Developmental NOAEL = 500 mg/kg/day LOAEL = 1,000 mg/kg/day
based on decreased fetal body weights
and reduced ossification of the sternebrae.
---- Reproduction and fertility effects.
DPX-JW062 Parental/Systemic NOAEL
= 1.5 mg/kg/day LOAEL = 4.4 mg/kg/day based on decreased
body weights, body weight gains, and food consumption
of F0 females, and
increased spleen weights in the F0
and F1 females Reproductive NOAEL = 6.4
mg/kg/day LOAEL = 6.4 mg/kg/day Offspring NOAEL = 1.5 mg/kg/day
LOAEL = 4.4 mg/kg/day based on decrease
in the body weights of the F1 pups during lactation.
---- Chronic toxicity rodents.
DPX-JW062 NOAEL = M 5, F 2.1
mg/kg/day LOAEL = M 10, F 3.6 mg/kg/day based on
decr. body weight, body weight gain, and food consumption
and food efficiency; decreased HCT,
HGB and RBC at 6 months in F[emales]
only. no evidence of carcinogenic potential
---- Chronic toxicity dogs
DPX-JW062 NOAEL = M 2.3, F 2.4
mg/kg/day LOAEL = M 18, F 19 mg/kg/day based on decr.
HCT, HGB and RBC; increased Heinz bodies and reticulocytes
and associated secondary microscopic
changes in the liver, kidneys, spleen, and bone marrow;
increased absolute and relative liver
weights.
---- Carcinogenicity mice
DPX-JW062 NOAEL = M 2.6, F4.0
mg/kg/day LOAEL = M 14, F 20 mg/kg/day based on decreased
body weight, body weight gain, and food efficiency
and clinical signs indicative of neurotoxicity.
No evidence of carcinogenicity
--- Metabolism and pharmacokinetics.
Both DPX-MP062 and DPX-JW062
were extensively metabolized and the metabolites were
eliminated in urine, feces, and bile. The metabolite profile
for DPX-JW062
was dose dependent and varied quantitatively between males
and females. Differences in metabolite profiles were
also observed for the different label positions (indanone
and trifluoromethoxyphenyl rings). All biliary metabolites
undergo further biotransformation in the gut. The proposed
metabolic pathway for both DPX-MP062
and DPX-JW062 has multiple metabolites bearing one
of the two ring structures (see 870- 4100 chronic toxicity
rodents above). |
Nov
27, 2002 |
OPP-2002-0313 |
EPA
approved the use of Indoxacarb for 1 Emergency Exemption.
--
Massachusetts: Crisis: On June 7, 2002,
for the use of indoxacarb on cranberry to control weevils.
This program ended on October 1, 2002. |
Sept
18, 2002 |
OPP-2002-0256 |
Pesticide
Tolerance for Emergency Exemption for residues on Craneberry
at 0.50 ppm in the state of Massachusetts. FINAL
RULE. This regulation establishes
a time-limited tolerance for combined residues of indoxacarb
in or on cranberry. The
tolerance will expire and is revoked on December 31, 2004.
-- The Massachusetts Department of Food and Agriculture have
indicated that populations of the cranberry weevil in the
state have developed resistance to the registered alternative,
chlorpyrifos. Without adequate control, this pest was expected
to result in significant crop damage and yield losses for
cranberry growers, leading to significant economic losses.
The state requested indoxacarb for this use, since field trials
have shown it to be effective at controlling this pest.
-- The nature of the toxic effects caused by indoxacarb, a
summary of the toxicological dose and endpoints for indoxacarb
for use in this human risk assessment, and the most recent
estimated aggregate risks resulting from registered uses are
discussed in the Federal Register for July 18, 2002 final
rule (see below) establishing tolerances for residues of indoxacarb
in/on alfalfa forage, alfalfa hay, peanut, peanut hay, potato,
soybean seed, soybean aspirated grain fractions, and soybean
hulls. |
July
18, 2002 |
OPP-2002-0105 |
DuPONT
- Pesticide
Tolerance. FINAL RULE. This regulation establishes
tolerances for combined residues of indoxacarb in or on alfalfa
forage, alfalfa hay, peanut, peanut hay, potato, soybean seed,
soybean aspirated grain fractions, and soybean hulls. Additionally,
the petition requested an increase in tolerance levels for
head lettuce, milk, milk fat, meat, fat, and meat by-products
of cattle, goat, hog, horse, and sheep based on a proposed
increase in the labeled use rate for head lettuce and on potential
changes in residue levels in livestock diets.
-- DPX-JW062. 90-Day oral toxicity
in nonrodents: NOAEL = 5.0 mg/kg/ day LOAEL = 19 mg/kg/ day
based on hemolytic anemia, secondary
histopathologic findings indicative of blood
breakdown (pigment in Kupffer cells, renal tubular
epithelium, and spleen and bone marrow macrophages); increase
in splenic EMH; and RBC hyperplasia in bone
marrow in dogs
-- DPX-MP062. 21/28-Day dermal
toxicity: changes in hematology
parameters (increased reticulocytes), the
spleen (increased absolute and relative weight M only,
gross discoloration), clinical signs of toxicity in both sexes
in rats.
-- DPX-JW062. Prenatal developmental
in nonrodents: LOAEL = 1,000 mg/kg/ day based on decreased
fetal body weights and reduced ossification
of the sternebrae
-- DPX-JW062. Reproduction and
fertility effects: LOAEL = 4.4 mg/kg/ day based on decreased
body weights, body- weight gains, and food consumption of
F0 females, and increased spleen weights
in the F0
and F1
females.
-- DPX-JW062. Chronic toxicity
Dogs: LOAEL = M 18, F 19 mg/kg/day based on decreased HCT,
HGB nd RBC; increased Heinz bodies and reticulocytes and associated
secondary microscopic changes in the
liver, kidneys, spleen, and bone marrow; increased absolute
and relative liver weights.
-- DPX-JW062. Carcinogenicity
mice: LOAEL = M 14, F 20 mg/kg/day based on decreased body
weight, body weight gain, and food efficiency and clinical
signs indicative of neurotoxicity No evidence of carcinogenicity.
-- DPX-JW062.
Other effects: cytotoxicity observed
at >50 [mu]g/mL
-- DPX-MP062.
Other effects: cytotoxicity was seen at concentrations
of >100 [mu]g/mL
-- Metabolism and pharmacokinetics:
The metabolite profile for DPX-JW062 was dose dependent and
varied quantitatively between males
and females. |
Jan 25, 2002 |
PF-1066 |
DuPONT
- Pesticide
Tolerance Petition; in or on in or on the raw agricultural
commodities: Alfalfa forage at 12 ppm, alfalfa hay at 50 ppm,
peanut at 0.01 ppm, peanut hay at 40 ppm, potato at 0.02 ppm,
soybean aspirated grain fractions at 70 ppm, soybean hulls
at 6.5 ppm, head lettuce at 5 ppm, meat (of cattle, goats,
hogs, horses and sheep) at 0.05 ppm, fat (of cattle, goats,
hogs, horses and sheep) at 1.5 ppm, meat by-products (of cattle,
goats, hogs, horses and sheep) at 0.03 ppm and milk at 0.15
ppm. |
Sept
29, 2000 |
OPP-301064 |
DuPONT
- Pesticide
Tolerances. - FINAL RULE. This regulation establishes
permanent tolerances for the combined residues of Indoxacarb
and its R-enantiomer in a 75:25 mixture (DPX-
MP062), respectively, in or on the raw agricultural
commodities as follows: apples, pears, Brassica (head and
stem subgroup), cotton, leaf lettuce, head lettuce, fruiting
vegetable group, sweet corn, milk, and the meat, meat byproducts
and fat of cattle, goats, horses, hogs and sheep. |
Mar
31, 1999 |
na |
DuPONT
- Experimental
Use Permit 352-EUP-166. This experimental use permit allows
the use of 82.5 pounds of the insecticide indoxacarb on 150
acres of cotton on a crop destruct basis to evaluate the control
of various insect pests. The program is authorized only in
the States of Alabama, Arkansas, Georgia, Louisiana, Mississippi,
North Carolina, Oklahoma, South Carolina, Tennessee, and Texas.
The experimental use permit is effective from March 9, 1999
to March 9, 2000. This permit is issued with the limitation
that all treated crops will be destroyed or used for research
purposes only. |
Apr
16, 1998 |
PF-802 |
DuPONT
- Pesticide
Petition to establish tolerances for residues of the insecticide
DPX-MP062 in/on the raw agricultural commodities as follows:
pome fruit at 2.0 ppm, apple pomace at 6.0 ppm, head and stem
brassicas at 10.0 ppm, cottonseed at 3.0 ppm, cotton gin trash
at 15.0 ppm, leaf lettuce at 20.0 ppm, head lettuce at 7.0
ppm, fruiting vegetables at 0.70 ppm, sweet corn kernel at
0.02 ppm, sweet corn forage at 20.0 ppm, and sweet corn stover
at 25.0 ppm, meat 0.02 ppm, milk at 0.10 ppm, cattle kidney
at 0.05 ppm; and by establishing a tolerance for residues
of the insecticide DPX-MP062
in/on milk fat at 0.75 ppm and cattle fat at 0.75 ppm. Three
analytical enforcement methods are available for determining
these plant and animal resi |
Apr
15, 1998 |
OPP-30449 |
- DuPONT
- Application
to register 3 pesticide products:
- 2.
File Symbol: 352-LOU. DPX-MP062.
Manufacturing Use Product/Insecticide. Active ingredient:
at 52.7 percent. For formulation purposes only.
- File
Symbol: 352-LOI. DPX-MP062
SC. Insecticide. Active ingredien at 15 percent. For
agricultural crop use to control certain pests.
- File
Symbol: 352-LOT. DPX-MP062
WG. Insecticide. Active ingredient at 30 percent. For
agricultural crop use to control certain pests.
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