Indoxacarb

Insecticides

Active substance -> EU Pesticides database: Not approved

Pesticides -> Other Insecticides

Insecticides

Environmental transformation -> Pesticides (parent, predecessor)

Pesticide (Indoxacarb) -> USDA PDB

Solubility in n-octanol 14.5 g/L, methanol 103 g/L, acetonitrile 139 g/L, acetone >250 g/kg (all at 25 °C)

In water, 0.20 mg/L at 20 °C

Positive

2.84

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

205.7 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID1032690]

207.03 Ų [M+H]+ [CCS Type: TW]

205.99 Ų [M+H]+

203.97 Ų [M+H]+ [CCS Type: TW; Buffer gas: N2; Ionization: GC-APCI+]

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P260, P261, P264, P270, P271, P272, P273, P280, P301+P316, P302+P352, P304+P340, P317, P319, P321, P330, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 3% (3 of 100) of reports.

Danger

H301 (97%): Toxic if swallowed [Danger Acute toxicity, oral]

Commission Regulation No 844/2012

Indoxacarb is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

06/10/EC, Reg. (EU) 2017/1511, Reg. (EU) 2018/1262, Reg. (EU) 2019/1589, Reg. (EU) 2020/1511, Reg. (EU) 2021/1449, Reg. (EU) 2021/2081, Reg. (EU) No 533/2013, Reg. (EU) No 540/2011

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: apple; apple, wet pomace; brassica, head and stem, subgroup 5A; alfalfa, forage; alfalfa, hay; cattle, fat; cattle, meat; cattle, meat byproducts; corn, sweet, forage; corn, sweet, kernel plus cob with husk removed; corn, sweet, stover; cotton gin byproducts; cotton, undelinted seed; goat, fat; goat, meat; goat, meat byproducts; hog, fat; hog, meat; hog, meat byproducts; horse, fat; horse, meat; horse, meat byproducts; lettuce, head; lettuce, leaf; milk; milk, fat; pear; peanut; peanut, hay; potato; sheep, fat; sheep, meat; sheep, meat byproducts; soybean, aspirated grain fractions; soybean, hulls; soybean, seed; and vegetable, fruiting, group 8.

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 will expire and are revoked on the dates specified: cherry, sweet (Expiration/revocation date May 21, 2007); cherry, tart (Expiration/revocation date May 21, 2007); and peach (Expiration/revocation date May 15, 2006).

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 will expire and are revoked on the dates specified: collards (Expiration/revocation date 6/30/06; and cranberry Expiration/revocation date 12/31/07).

Acute Tox. 3 (97%)

Acute toxicity - category 3

Acute toxicity (Oral) - Category 4

Acute Tox. 3

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

The protective clothing should be kept in separate places where it cannot be contaminated with toxic chemicals. It should be forbidden to keep this clothing in living quarters. Protective clothing must be washed at least once a week and each time it is contaminated with pesticides. Before washing the clothing should be soaked for several hours in a calcium carbonate solution. /Pesticides/

Smoking, eating, and drinking before washing should be absolutely prohibited when any pesticide ... is being handled or used. /Pesticides/

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: apple, 1.0 ppm; apple, wet pomace, 3.0 ppm; brassica, head and stem, subgroup 5A, 5.0 ppm; alfalfa, forage, 10 ppm; alfalfa, hay, 50 ppm; cattle, fat, 1.5 ppm; cattle, meat, 0.05 ppm; cattle, meat byproducts, 0.03 ppm; corn, sweet, forage, 10 ppm; corn, sweet, kernel plus cob with husk removed, 0.02 ppm; corn, sweet, stover, 15 ppm; cotton gin byproducts, 15 ppm; cotton, undelinted seed, 2.0 ppm; goat, fat, 1.5 ppm; goat, meat, 0.05 ppm; goat, meat byproducts, 0.03 ppm; hog, fat, 1.5 ppm; hog, meat, 0.05 ppm; hog, meat byproducts, 0.03 ppm; horse, fat, 1.5 ppm; horse, meat, 0.05 ppm; horse, meat byproducts, 0.03 ppm; lettuce, head, 5.0 ppm; lettuce, leaf, 10 ppm; milk, 0.15 ppm; milk, fat, 4.0 ppm; pear, 0.20 ppm; peanut, 0.01 ppm; peanut, hay, 40 ppm; potato, 0.01 ppm; sheep, fat, 1.5 ppm; sheep, meat, 0.05 ppm; sheep, meat byproducts, 0.03 ppm; soybean, aspirated grain fractions, 45 ppm; soybean, hulls, 4.0 ppm; soybean, seed, 0.80 ppm; and vegetable, fruiting, group 8, 0.50 ppm.

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 will expire and are revoked on the dates specified: cherry, sweet 1.0 ppm (Expiration/revocation date May 21, 2007); cherry, tart 1.0 ppm (Expiration/revocation date May 21, 2007); and peach 10 ppm (Expiration/revocation date May 15, 2006).

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 will expire and are revoked on the dates specified: collards 3.0 ppm (Expiration/revocation date 6/30/06; and cranberry 0.50 ppm (Expiration/revocation date 12/31/07).

Very few case reports of acute indoxacarb ingestion are reported in the literature. Reported treatments commonly involve treatment with methylene blue (A15205) (A15207) (A15206). Severe metabolic acidosis was treated with continuous veno-venous hemofiltration (CVVHF) and bicarbonate (NaHCO3) (A15207).

Acute ingestion of indoxacarb causes methemoglobinemia (A15205). Indoxacarb poisoning has also been associated with acute kidney injury, involving acute renal failure and severe metabolic acidosis (A15207). A case involving rhabdomyolysis, in addition to methemoglobinemia and acute kidney injury, has also been reported (A15206).

LD50 Colinus virginianus (Bobwhite quail) oral 98 mg/kg /DPX-MP062, 3:1 mixture of (S) and (R) isomers/

LC50 Anas platyrhynchos (Mallard duck) dietary >5620 ppm/5 days /DPX-MP062, 3:1 mixture of (S) and (R) isomers/

LC50 Colinus virginianus (Bobwhite quail) dietary 808 ppm/5 days /DPX-MP062, 3:1 mixture of (S) and (R) isomers/

LC50 Daphnia 0.60 mg/L/48 hr /Conditions of bioassay not specified in source examined/ /DPX-MP062, 3:1 mixture of (S) and (R) isomers/

For more Ecotoxicity Values (Complete) data for INDOXACARB (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8,100(SRC), determined from a log Kow of 4.65(2) and a regression-derived equation(3), indicates that indoxacarb is expected to be immobile in soil(SRC). Volatilization of indoxacarb from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.6X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 1.9X10-10 mm Hg(2), and water solubility, 0.20 mg/L(2). Indoxacarb is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). Biodegradation data were not available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8,100(SRC), determined from a log Kow of 4.65(2) and a regression-derived equation(3), indicates that indoxacarb is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 6.6X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 1.9X10-10 mm Hg(2), and water solubility, 0.20 mg/L(2). According to a classification scheme(4), an estimated BCF of 2,000(SRC), from an estimated log Kow(2) and a regression-derived equation(5), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Aqueous hydrolysis half-lives measured for indoxacarb were greater than 30 days at pH 5, 38 days at pH 7, and 1 day at pH 9(2). Biodegradation data were not available(SRC, 2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), indoxacarb, which has a vapor pressure of 1.9X10-10 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase indoxacarb may be removed from the air by wet and dry deposition(SRC).

It is thought that indoxacarb's aromatic metabolites biotransform to active intermediates that produce methemoglobin (A15207). The mechanism of indoxacarb-induced renal injury and metabolic acidosis in humans remains unclear. (A15207) It has been suggested that acute kidney injury results from indoxacarb-induced circulatory shock (A15206). Rhabdomyolysis may have been induced by methemoglobinemia (A15206).

Human toxicity includes eye irritation, blurred vision, skin sensitization with allergic rashes, alteration in blood cell counts, and/or anemia (A15205). As methemoglobin levels increase, typical symptoms develop. Levels of 20 – 50% will cause respiratory distress, dizziness, headache, and fatigue as in this case. Lethargy and stupor develop at levels around 50% and death may occur around 70%. (A15206)

The Koc of indoxacarb is estimated as 8,100(SRC), using a log Kow of 4.65(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that indoxacarb is expected to be immobile in soil.

An estimated BCF of 2,000 was calculated for indoxacarb(SRC), using an estimated log Kow of 4.65(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not altered physically or chemically once released into the environment.

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: apple; apple, wet pomace; brassica, head and stem, subgroup 5A; alfalfa, forage; alfalfa, hay; cattle, fat; cattle, meat; cattle, meat byproducts; corn, sweet, forage; corn, sweet, kernel plus cob with husk removed; corn, sweet, stover; cotton gin byproducts; cotton, undelinted seed; goat, fat; goat, meat; goat, meat byproducts; hog, fat; hog, meat; hog, meat byproducts; horse, fat; horse, meat; horse, meat byproducts; lettuce, head; lettuce, leaf; milk; milk, fat; pear; peanut; peanut, hay; potato; sheep, fat; sheep, meat; sheep, meat byproducts; soybean, aspirated grain fractions; soybean, hulls; soybean, seed; and vegetable, fruiting, group 8.

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 will expire and are revoked on the dates specified: cherry, sweet (Expiration/revocation date May 21, 2007); cherry, tart (Expiration/revocation date May 21, 2007); and peach (Expiration/revocation date May 15, 2006).

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 will expire and are revoked on the dates specified: collards (Expiration/revocation date 6/30/06; and cranberry Expiration/revocation date 12/31/07).

... Indoxacarb inhibits sodium channels and certain subtypes of nicotinic receptors.

The effects of the oxadiazine insecticide indoxacarb and its N-decarbomethoxylated metabolite (DCJW) on tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal ganglion neurons were studied using the whole-cell patch clamp technique. Indoxacarb and DCJW suppressed the peak amplitude of action potentials, and DCJW exhibited a faster time course and higher potency than indoxacarb in the blocking effects. In voltage-clamp experiments, indoxacarb and DCJW suppressed TTX-R sodium currents in a time-dependent manner without a steady-state level of suppression. IC50 values for indoxacarb and DCJW on TTX-R sodium currents were estimated to be 10.7 and 0.8 microM after 25 min of bath application, respectively. DCJW was about 10 times more potent than indoxacarb in blocking TTX-R sodium currents. Although the suppressive effects of indoxacarb were partially reversible after washout with drug-free external solution, no recovery of sodium current was observed in DCJW treated neurons after prolonged washout. In current-voltage relationships, both indoxacarb and DCJW blocked the sodium currents to the same degree in the entire range of membrane potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by indoxacarb and DCJW at 10 microM. In contrast, the steady-state inactivation curves were shifted in the hyperpolarizing direction by indoxacarb as well as by DCJW. Based on these results, it was concluded that indoxacarb and DCJW potently blocked the TTX-R sodium channel in rat DRG neurons with hyperpolarizing shifts of the steady-state inactivation curves, suggesting preferential association of the insecticides to the inactivated state of sodium channels. The small structural variation between indoxacarb and DCJW resulted in clear differences in potency for blocking sodium channels and reversibility after washout.

Metabolism in rats after oral dosing was studied using both DPX-JW062 and DPX-MP062. Most of the dose was excreted within 96 hr. Extensive metabolism to numerous minor metabolites occurs. In urine, metabolites were cleaved products (indane or trifluoromethoxyphenyl ring products), whilst in feces, major metabolites retained both these moieties. Major metabolic reactions included hydroxylation of the indane ring, hydrolysis of the carboxymethyl group from the amino nitrogen, and opening of the oxadiazine ring, which gave rise to cleaved products.

Metabolism in rats after oral dosing noted that most of the dose was excreted within 96 h. In urine, metabolites were cleaved products (indane or trifluoromethoxyphenyl ring products), whereas in feces, major metabolites retained both these moieties. Major metabolic reactions included hydroxylation of the indane ring, hydrolysis of the carboxymethyl group from the amino nitrogen, and opening of the oxadiazine ring, which gave rise to cleaved products. (A15205)

Used as broad spectrum insecticide in cotton, vegetables, and fruit; [HSDB] A new reduced risk pesticide to replace organophosphates; Proposed for use on apples, pears, Brassica, sweet corn, lettuce, and fruiting vegetables to control insects, including the beet armyworm; [Reference #1]

Farming (Pesticides) [Category: Industry]

For indoxacarb (USEPA/OPP Pesticide Code: 067710) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Insecticide

Broad spectrum control of lepidoptera and certain other pests in cotton, vegetables, and fruit.

This is a man-made compound that is used as an insecticide.

Dispersible granule; suspension concentrate.

DPX-JW062 is a 1:1 mixture of the (active) (S)- and (inactive) (R)- isomers; DPX-MP062 is a 3:1 mixture of these isomers. The pure (S)- isomer is referred to as DPX-KN128, the (R)- isomer as DPX-KN127.

Trade names: Avaunt, Steward, Avatar, Rumo, Tornado

Insecticides

Environmental transformation -> Pesticides (parent, predecessor)