Indoxacarb
CAS No. 173584-44-6
US Federal Register
 
 

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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:

US Federal Register

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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