Carboxin

235.3

235.30

226-031-1

5A8K850HDE

263492

DTXSID0023951

CRYSTALS FROM ETHANOL OR METHANOL|WHITE SOLID|Off-white crystalline solid

2934999038

63.6

2.3

White Crystals

1.7 g/mL

93-95 °C

420.6±45.0 °C at 760 mmHg

100 °C

1.636

H2O: 10.095 g/100 mL

0-6°C

2.5 x 10 -5 Pa (25 °C)

Oral-Rat LD50: 430 mg/kg; Oral-Mouse LD50: 3200 mg/kg

Combustion produces toxic nitrogen oxide and sulfur oxide gas

Henry's Law constant = 3.2X10-10 atm-cu m/mol at 25 °C (est)

149.35 Ų [M+H]+ [CCS Type: TW]

Colorless solid; mp: 91.5-92.5 °C; a dimorphic form has mp: 98-100 °C; vp: <133 Pa (20 °C); solubility (25 °C): 170 mg/l water; 600 g/kg acetone; 1500 g/kg dimethyl sulfoxide; 110 g/kg ethanol; 210 g/kg methanol. /Technical carboxin (>97% pure)/|Hydroxyl radical reaction rate constant = 1.3X10-10 cu cm/molec-sec at 25 °C (est)

No rapid reaction with air. No rapid reaction with water.

Amides and Imides

Non-corrosive

NONH for all modes of transport

3

21/22-36/37/38-20/21/22

36-26

RP4550000

Xi,Xn

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

Chemically very stable, except to strong acids and alkalis.

P260, P261, P264, P270, P272, P273, P280, P301+P312, P302+P352, P314, P321, P330, P333+P313, P363, P391, P501

H302

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.|Carboxin is resistant to mild oxidative and hydrolytic conditions. Alkaline hydrolysis yields the more toxic aniline. If reuse is not possible, incineration appears to be the method of choice for disposal. Recommendable method: Incineration. Not recommendable method: Alkaline hydrolysis.

USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Carboxin. EPA 738-R-04-015 September 2004. Available from the Database Query page at http://cfpub.epa.gov/oppref/rereg /status.cfm?show=rereg as of April 22, 2005. The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the U.S.|California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summaries. Available from: http://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm on Carboxin (5234-68-4) as of April 21, 2005.

|Warning|H302 (28.86%): Harmful if swallowed [Warning Acute toxicity, oral]|P260, P261, P264, P270, P272, P273, P280, P301+P312, P302+P352, P314, P321, P330, P333+P313, P363, P391, and P501|Aggregated GHS information provided by 150 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Approved respirator. Chemical-resistant gloves. Long-sleeved shirt and long pants. Protective eyewear. Hat. Waterproof boots.

Avoid contact with skin or clothing. Wash hands and face thoroughly with soap and water after use and before eating or smoking.|SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|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.

Contact with eyes can cause irritation.

moderately toxic

LD50 Rabbit percutaneous >4000 mg/kg|LC50 Rat inhalation >4.7 mg/L air/4 hr|LD50 Hen oral 24000 mg/kg|LD50 Mouse oral 3200 mg/kg|For more Non-Human Toxicity Values (Complete) data for CARBOXIN (6 total), please visit the HSDB record page.

/BIRDS and MAMMALS/ Following chronic exposure, mallard ducks (Anas platyrhynchos) exhibited reductions in the number of eggs laid, viable embryos, live 3-week embryos, normal hatchlings and 14-day survivors at 700 mg/kg/day.|/AQUATIC SPECIES/ /In/ two freshwater fish toxicity studies... Rainbow trout exposed to the four highest concentration levels (0.93, 1.5, 2.4, and 4.1 mg/L) demonstrated partial to complete loss of equilibrium, lethargy, darkened pigmentation and swimming on the surface. ...Bluegill sunfish exposed to the three highest concentrations, i.e., 2.7, 4.3, and 7.5 mg/L, also demonstrated partial to complete loss of equilibrium, lethargy, darkened pigmentation and swimming on the surface.

Carboxin's production may result in its release to the environment through various waste streams; it's use as a fungicide for commercial seed treatment and on-farm seed treatment(1) will result in its direct release to the environment(SRC).

Terrestrial Fate: Five different soils varying in physiochemical properties were studied for the persistence & degradation of carboxin & oxycarboxin. In one soil only, both were degraded with accumulation of ammonium & nitrite. Under conditions of forced circulation of air & continuous perfusion, oxycarboxin was more susceptible to degradation than carboxin. Under simulated rice field conditions, conversion of carboxin to its sulfoxide & to a nontoxic derivative of oxycarboxin was observed in all soils. Carboxin was rapidly converted to its sulfoxide on 3 forms of monoionic clays.|TERRESTRIAL FATE: Based on a classification scheme(1), a measured Koc value of 71(2), indicates that carboxin is expected to have high mobility in soil(SRC). Volatilization of carboxin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.2X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 1.5X10-7 mm Hg(3), and water solubility, 147 mg/L(3). Carboxin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). The mean half-lives of carboxin in aerobic and anaerobic soil metabolism studies were 1.25 and 129 days, respectively(2).|AQUATIC FATE: Based on a classification scheme(1), a measured Koc value of 71(2), indicates that carboxin is not 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 3.2X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 1.5X10-7 mm Hg(4), and water solubility, 147 mg/L(4). According to a classification scheme(5), an estimated BCF of 9(SRC), from a log Kow of 2.3(4) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low. Carboxin did not undergo hydrolysis in aqueous buffered solutions at pH 5,7, and 9(2). A photolysis half-life of 1.5 hours was observed when carboxin in distilled water was irradiated with light from a xenon arc lamp(2), suggesting that photolysis in sunlit surface water may be an important environmental fate process. The half-life of carboxin in aerobic and anaerobic aquatic metabolism studies were 34 days and 239 days, respectively(2).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), carboxin, which has a vapor pressure of 1.5X10-7 mm Hg at 25 °C(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase carboxin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone molecules(SRC). The half-life for this reaction with hydroxyl radicals is estimated to be about 3 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C and the half-life for this reaction with atmospheric ozone is approximately 5 hours calculated from its rate constant of 5.7X10-17 cu cm/molecule-sec at 25 °C(3). Particulate-phase carboxin may be removed from the air by wet and dry deposition(SRC). Vapor-phase carboxin may also undergo direct photolysis in the atmosphere, based on an aqueous photolysis half-life of 1.5 hours in measured distilled water(4).

The rate constant for the vapor-phase reaction of carboxin with photochemically-produced hydroxyl radicals has been estimated as 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the reaction of carboxin with atmospheric ozone has been estimated as 5.7X10-17 cu cm/molec-sec using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Carboxin was stable to hydrolysis at pH 5, 7 and 9 at 25 °C; however, photolysis in aqueous solutions is rapid, with a half-life of approximately 1.5 hours in distilled water(3). Under simulated sunlight conditions, carboxin in aqueous solution degraded rapidly with a half-life of 1.9 hours producing carboxin sulfoxide and oxanilic acid as metabolites(4). This reaction was shown to be enhanced with the addition of humic and fulvic acids(4).

An estimated BCF of 9 was calculated for carboxin(SRC), using a log Kow of 2.3(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

257.04 L/kg|Carboxin adsorption and desorption isotherms were estimated using a Manchester sandy loam(1). An adsorption Fruendlich coefficient of 0.78 with a 1/n value of 0.93 was calculated from the adsorption data using linear regression on log transformed data. The desorption isotherm had a Fruendlich coefficient of 1.1 with 1/n of 0.94. The organic carbon content of the soil was 1.09%, corresponding to a Koc of 71(1). According to a classification scheme(2), this Koc value suggests that carboxin is expected to have high mobility in soil(SRC). Twenty inches of water was eluted through a 12 inch column of a clay loam soil to which 14C labeled carboxin had been applied(1). Fifty-two percent of the applied radioactivity and 41% of the applied carboxin were found in the leachate. Thirty-eight percent of the radioactivity remained in the column and ten percent of the radioactivity could not be accounted for at the end of the study(1). This soil column leaching study suggests that carboxin is highly mobile(SRC).

The Henry's Law constant for carboxin is estimated as 3.2X10-10 atm-cu m/mole(SRC) derived from its vapor pressure, 1.5X10-7 mm Hg(1), and water solubility, 147 mg/L(1). This Henry's Law constant indicates that carboxin is expected to be essentially nonvolatile from water surfaces(2). Carboxin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

SURFACE WATER: Based upon a search of the EPA STORET database, from 2000-2005, carboxin was monitored for, but not detected in 30 surface water samples from Arizona(1).

Carboxin was identified, not quantified, in food residues during a monitoring period of 1978-1982(1). Carboxin was also identified, not quantified, (detection limit 0.01 ppm) during 1990 regulatory monitoring of foods by the FDA(2).

Occupational exposure to carboxin may occur through inhalation and dermal contact with this compound at workplaces where it is produced and used. There is potential inhalation and dermal exposure to workers who treat seed with carboxin in both commercial and on-farm settings(1). Seven major exposure scenarios were identified as representative of carboxin use : 1) farm seed treatment with dry formulations - open transfer systems, 2) on farm seed treatment with liquid formulations - closed transfer system, 3) loading and applying liquid with commercial seed-treatment equipment, 4) bagging and otherwise handling treated seeds with commercial equipment, 5) commercial sewer stitching bags of seed, 6) multiple commercial seed treatment activities and 7) loading and planting treated seeds(1). The EPA has assessed the dietary risk posed by carboxin and determined that carboxin exposure to the general population from food and water are well below the Agency's level of concern for all populations(1).

Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. (See all compounds classified as Fungicides, Industrial.)

Carboxin and its sulfoxide are absorbed by germinating seeds and moved upward in the plant, traveling with transpiration system and moving into the lower stem and first leaves of the plant. Carboxin does not redistribute into new growth as the plant develops, and is not found in the seeds or upper leaves of crops grown from treated seed. Animals excrete carboxin and its degradation products rapidly, and no accumulation in tissues was indicated.|When carboxin was applied to bean plants (phaseolus vulgaris leguminatate ) ... most of fungicide residue in roots was in form of acetone-insol material. ... Barley plants formed carboxin-lignin complexes in the leaves.|When fed to dogs, carboxin is partially oxidized to oxycarboxin. Both compounds are excreted in urine.|Extensively metabolized in rats and eliminated mainly in urine and to a lesser extent feces.|Rats have been reported to excrete almost an entire dose within 24 hr, primarily in the urine.

In dogs fed carboxin, oxidation to sulfoxide occurred ... .|Rats and rabbits hydroxylated the phenyl ring of carboxin to give mainly para- and ortho-isomers. They were excreted in urine as glucuronides in rabbits (62 and 10%) and rats (26 and 6%); only traces of meta-isomer conjugate were detected. Variable amounts (1-15%) of the free para-isomer were found in feces of rats, but not of rabbits. A common minor urinary metabolite was identified tentatively as the sulfoxide of one of the phenols (1-3%). The remainder of the dose was unchanged carboxin in the feces (rat, 41%; rabbit, 10%) and in the urine (1-2%).|Extensively metabolized in rats... . Major metabolites in urine are p-hydroxylated carboxin sulfoxide, 4-acetamidophenol and its O-glucuronide.|/In plants,/ undergoes oxidation to carboxin sulfoxide and carboxin sulfone.|For more Metabolism/Metabolites (Complete) data for CARBOXIN (7 total), please visit the HSDB record page.

Carboxin was tested for its effects on the activities of mitochondria from fungi. At low concentrations it inhibited mitochondrial succinate oxidation from the sensitive fungus Ustilago maydis. The inhibition was of the noncompetitive nature. It is believed that carboxin inhibits mitochondrial respiration at or close to the site of succinate oxidation and does not greatly affect the remaining portion of the electron transport system or the coupled phosphorylation reactions.|The sequence of an allele encoding the iron sulfur protein subunit of succinate dehydrogenase was determined following PCR amplification of genomic DNA from a carboxin sensitive Ustilago maydis strain. Comparison of this sequence with that of the iron sulfur protein allele from a carboxin resistant strain revealed a two base difference between the sequences. This mutation led to the substitution of a leucine residue for a histidine residue within the third cysteine rich cluster of the deduced amino acid sequence of the carboxin resistant strain allele. This cluster, which is associated with the S3 iron redox center, is involved in the transport of electrons from succinate to ubiquinone. Confirmation that this nucleotide change led to enhanced resistance to carboxin was obtained following mutagenesis of the sensitive iron sulfur protein allele to the resistant form and expression of the mutated allele in Ustaligo maydis.|The compounds /carboxin and oxycarboxin/ inhibit oxidative metabolism and succinic dehydrogenase in mitochondria of liver and bone.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/CASE REPORTS/ ...A 7-year-old boy /ingested/ several handfuls of carboxin-treated wheat seed. Symptoms included vomiting and headache which developed within 1 hr but were rapidly resolved after administration of an emetic. The amount of carboxin consumed is unclear.

5,6-Dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide

A FLOWABLE LIQUID FORMULATION CONTAINING 17.3% VITAVAX BY WT & 15.4% THIRAM BY WT IS REGISTERED IN CANADA AS VITAFLO; ALSO AS A DRY POWDER DRILL BOX FORMULATION CONTAINING 40% THIRAM & 40% VITAVAX (VITAFLO DB).|VITAVAX-200 (37-5% CARBOXIN, 37.5% THIRAM); VITAVAX 75% (34% CARBOXIN); VITAVAX-300 (37.5% CARBOXIN, 37.5% CAPTAN).|Technical grade is >97% pure.|Seed treatment; wettable powder; suspension concentrate; flowable concentrate for seed treatment.|For more Formulations/Preparations (Complete) data for CARBOXIN (24 total), please visit the HSDB record page.

It was introduced in 1966 by Uniroyal as experimental systemic seed treatment fungicide.|Secondary benefit of seed treatment is protection of germinating seeds & young seedlings from soilborne fungi that cause seed decay, seedling blights (damping-off) & root rots. /Fungicides/|Do not use treated grain as animal or human food.|Its apparent mode of action is to selectively concentrate in fungal cells, where it inhibits succinic dehydrogenase, a respiratory enzyme in the mitochondria.|For more General Manufacturing Information (Complete) data for CARBOXIN (6 total), please visit the HSDB record page.

/Analysis is by/ infrared absorption measurements of solution of 5.97, 6.30, & 7.75 U. Hydrolysis to aniline & colorimetric determination with N(1-naphthyl)ethylenediamine dihydrochloride.|Product analysis is by HPLC or IR spectroscopy. Residue analysis is by hydrolysis to aniline and determination by colorimetry of a derivative (green tissue) or (for seed) by GLC.|Relative retention time data for carboxin and its metabolites for a 15 m SE-30 capillary GC column under a single temperature-programmed regime is presented.|Determination of carboxin was done using iodine azide. Hydrogen chloride, sodium azide and iodine were added to a solution of carboxin in water and the excess of iodine was titrated with sodium arsenite. Carboxin in soil samples was determined upon extraction with acetone.|For more Analytic Laboratory Methods (Complete) data for CARBOXIN (7 total), please visit the HSDB record page.

Determination of carboxin residues in animal tissue, milk, and eggs spectrophotometrically to form a colored product. The method is based on alkaline hydrolysis of carboxin and its sulfoxide metabolite to produce aniline. The procedure for milk is essentially the same as that for meat, except that the milk samples are freeze dried before extraction with aqueous acetone. Sensitivity is 0.2 ppm. Recoveries were 77-84% for liver and 77-86% for milk.

Agrochemicals -> Fungicides|Environmental transformation -> Pesticides (parent, predecessor)

Carboxin has known environmental transformation products that include carboxin sulfoxide, oxathiine amide sulfone, oxathiine amide sulfoxide, and oxycarboxin.|Carboxin has known environmental transformation products that include Carboxin M1 (P/V-10), Carboxin M12-P, Carboxin M13 P/V-54, Carboxin M14 P/V-55, Carboxin M5/M7, diastereomers, Carboxin M6, Carboxin M8, Carboxin M9, Carboxin sulfone M0, and Carboxin sulfoxide P/V-16 M4.