1,2,3,6-Tetrahydrophthalimide

151.163

151.16

201-602-8

59011

DTXSID8026513

Crystals from ethanol

2925190090

46.17000

0.22

1.2±0.1 g/cm3

135-136.5 °C

145 °C @ Press: 1.0 Torr

165.0±28.0 °C

1.533

In water, 4.18X10+4 mg/L at 25 deg C (est)

1.19X10-7 mm Hg at 25 deg C (est)

Henry's Law constant = 3.05X10-8 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 7.8X10-11 cu cm/molecule-sec at 25 °C (est)

II

8

UN 2922 8/PG 2

2

S61

P264, P270, P280, P301+P312, P305+P351+P338, P330, P337+P313, P501

H302

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.

Euopean Chemicals Bureau; IUCLID Dataset for 1,2,3,6-Tetrahydrophthalimide (85-40-5) contains information on use, toxicology, and environmental effects of this chemical as supplied to the European Union by industry.[Available from, as of March 3, 2011: http://ecb.jrc.ec.europa.eu/iuclid-datasheet/85405.pdf]

1,2,3,6-Tetrahydrophthalimide was detected on clothing of captan field applicators at a range of 0.02 (shin) to 2.39 (gloves) ug/sq cm(1).

1,2,3,6-Tetrahydrophthalimide's production and use as a chemical intermediate(1) may result in its release to the environment through various waste streams; it's formation as a metabolite of the fungicide Captan(2) will result in 1,2,3,6-tetrahydrophthalimide's direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that 1,2,3,6-tetrahydrophthalimide is expected to have very high mobility in soil(SRC). Volatilization of 1,2,3,6-tetrahydrophthalimide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.0X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 1,2,3,6-Tetrahydrophthalimide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Utilizing the Japanese MITI test, 0% of the Theoretical BOD was reached in 4 weeks(5) indicates that biodegradation is not a rapid environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that 1,2,3,6-tetrahydrophthalimide 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 3.0X10-8 atm-cu m/mole((SRC), developed using a fragment constant estimation method(4). Bioconcentration in aquatic organisms is low(5). Utilizing the Japanese MITI test, 0% of the Theoretical BOD was reached in 4 weeks(5) indicates that biodegradation is not a rapid environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,2,3,6-tetrahydrophthalimide, which has an estimated vapor pressure of 1.2X10-7 mm Hg at 25 °C((SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases. Vapor-phase 1,2,3,6-tetrahydrophthalimide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.6 hrs(SRC), calculated from its rate constant of 7.8X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 1,2,3,6-Tetrahydrophthalimide does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 1,2,3,6-tetrahydrophthalimide with photochemically-produced hydroxyl radicals has been estimated as 7.8X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of 1,2,3,6-tetrahydrophthalimide with ozone has been estimated as 7.0X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.3 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). 1,2,3,6-Tetrahydrophthalimide is expected to undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(3). 1,2,3,6-Tetrahydrophthalimide does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Using a partition coefficient test the BCF in in aquatic organisms is low(1).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1,2,3,6-tetrahydrophthalimide can be estimated to be 20(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,2,3,6-tetrahydrophthalimide is expected to have very high mobility in soil.

The Henry's Law constant for 1,2,3,6-tetrahydrophthalimide is estimated as 3.0X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates from water and moist soil surfaces(2). 1,2,3,6-Tetrahydrophthalimide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-7 mm Hg(SRC), determined from a fragment constant method(3).

Results of a survey of total tetrahydrophthalimide in baby foods(1).

Occupational exposure to 1,2,3,6-tetrahydrophthalimide may occur through inhalation and dermal contact with this compound at workplaces where 1,2,3,6-tetrahydrophthalimide is produced or used. A study of workers in captan-treated grape fields in California indicated exposure to 1,2,3,6-tetrahydrophthalimide with up to 114 ug/cu m being detected during mixing/loading operations of captan(1). Limited monitoring data indicate that the general population may be exposed to 1,2,3,6-tetrahydrophthalimide via ingestion of contaminated food that had been treated with the fungicide captan(SRC).

1,2,3,6-Tetrahydrophthalimide is a urinary metabolite of captan, a foliar fungicide used on many crops in California, particularly strawberries and grapes. The compound was detected in personal air samples of pesticide applicators at a range of 0.9 to 15.5 ug/cu m. Urine levels ranged from 0.024 to 0.059 ppm(1).

TPI given orally to rats in dosage of 230 mg/kg & (14)C observed. 75% (14)C excreted in urine and 15% in feces 48 hr after treatment.

... Five possible metabolites of captan: 1,2,3,6-tetrahydrophthalimide (THPI), cis-3-hydroxy-1,2,3,6-tetrahydrophthalimide (C3), cis-5hydroxy-1,2,3,6-tetrahydrophthalimide (C5), trans-3-hydroxy-1,2,3,6-tetrahrahydrophthalimide (T3), and trans-5-hydroxy-1,2,3,6-tetrahydrophthalimide (T5) ...|The use of tetrahydrophthalimide (85405) (THPI) and 2-thiothiazolidine-4-carboxylic-acid (TTCA) as potential parameters for the biological monitoring of occupational exposure to captan (133062). Male Wistar-rats were treated orally with 400, 814, and 1250 mg/kg and intraperitoneally with 20, 50 and 75mg/kg. Urine was collected for 48 hours in metabolism cages. Urine spot samples were collected from eight male fruit growers after spraying captan and from six nonexposed men. Capillary gas chromatography in combination with mass or sulfur selective detection was suitable for the qualitative and quantitative determination of THPI and TTCA in rat and human urine. The cumulative urinary excretion of THPI and TTCA accounted for about 5% of the delivered dose of captan. In nonexposed subjects, neither THPI nor TTCA could be detected using the currently available techniques. Occupational exposure to captan resulted in detectable excretion of both TTCA and THPI in urine. The authors conclude that THPI and TTCA have promise as parameters for the biological monitoring of occupational exposure to captan.|Feeding 54% LD50 dose of captan to rats produced 2 metabolites in the blood: tetrahydrophthalimide and tetrahydrophthalic acid.

/SRP:/ Immediate first aid: Remove patient from contact with the material. Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Dithiocarbamates and Related Compounds/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. 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 0.9% saline (NS) 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. Administer activated charcoal ... . /Dithiocarbamates and Related Compounds/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Use moderate hyperventilation (rate of 20 respirations per minute) if signs of cerebral edema are present. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Dithiocarbamates and Related Compounds/

/BIOMONITORING/ The contribution of dermal and respiratory exposure to captan (133062) to levels of tetrahydrophthalimide (85405) (THPI) in urine was studied among 26 fruit growers applying captan in orchards in the Netherlands. The workers used an air blast sprayer pulled by a tractor to treat an orchard. Personal air samples were used to assess pesticide particle concentrations. Skin pads were used to measure dermal exposure. Skin pads and air samples were analyzed for captan levels using high performance liquid chromatography. Urine samples were collected and analyzed for THPI by gas chromatography with chemical ionization and mass spectrometry. Estimates of total dermal exposure were based on extrapolation to total body exposures from skin pad exposures and compared to estimates based on exposure of skin pads on specific body areas. The highest dermal exposure was on the forehead, followed by the wrists and neck. Average air spraying duration was 211 minutes with a standard deviation of 84 minutes. The amount of captan handled per spraying varied from 1.7 to 22.5 kilograms. Respiratory exposure to captan was not found to contribute to urinary THPI; however, a clear association with urinary THPI was found from the estimations of exposure on the skin pads from the ankles and neck. Other factors such as use of a cabin on the tractor, wearing of gloves during mixing and loading, and the use of rubber boots also correlated very well in THPI in the urine. The authors conclude that dermal exposure data can be better linked to biological monitoring based on empirical findings as gathered in a pilot study rather than on estimates of total skin dose.|/BIOMONITORING/ ... Occupational exposure to captan resulted in detectable excretion of both 2-thiothiazolidine-4-carboxylic-acid (TTCA) and tetrahydrophthalimide (THPI) in urine. The authors conclude that THPI and TTCA have promise as parameters for the biological monitoring of occupational exposure to captan.

cis-4-cycloxexene-1,2-dicarboximide

ESSENTIALLY 100% AS A CHEMICAL INTERMEDIATE

1H-Isoindole-1,3(2H)-dione, 3a,4,7,7a-tetrahydro-: INACTIVE|A method for destruction of captan usuitable for use is discussed. Captan was decomposed to nontoxic tetrahydrophthalimide..

Determinations of captan and two metabolites in milk and meat are performed using gas-liquid chromatography.|Thin-layer chromatography & gas-liquid chromatography methods devised for separation of captan & tetrahydrophthalimide & other related compounds.

Transformation products|Environmental transformation -> Pesticide transformation products (metabolite, successor)

THPI is a known environmental transformation product of Captan.